Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genotypes”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,351 records · Page 75Linked to original sources
PubMed2006

HLA-DQB1 genotypes, islet antibodies and beta cell function in the classification of recent-onset diabetes among young adults in the nationwide Diabetes Incidence Study in Sweden.

AIMS/HYPOTHESIS: The World Health Organization considers an aetiological classification of diabetes to be essential. The aim of this study was to evaluate whether HLA-DQB1 genotypes facilitate the classification of diabetes as compared with assessment of islet antibodies by investigating young adult diabetic patients. SUBJECTS AND METHODS: Blood samples were available at diagnosis for 1,872 (90%) of the 2,077 young adult patients (aged 15-34 years old) over a 5-year period in the nationwide Diabetes Incidence Study in Sweden. Islet antibodies were measured at diagnosis in 1,869 patients, fasting plasma C-peptide (fpC-peptide) after diagnosis in 1,522, while HLA-DQB1 genotypes were determined in 1,743. RESULTS: Islet antibodies were found in 83% of patients clinically considered to have type 1 diabetes, 23% with type 2 diabetes and 45% with unclassifiable diabetes. After diagnosis, median fpC-peptide concentrations were markedly lower in patients with islet antibodies than in those without (0.24 vs 0.69 nmol/l, p<0.0001). Irrespective of clinical classification, patients with islet antibodies showed increased frequencies of at least one of the risk-associated HLA-DQB1 genotypes compared with patients without. Antibody-negative patients with risk-associated HLA-DQB1 genotypes had significantly lower median fpC-peptide concentrations than those without risk-associated genotypes (0.51 vs 0.74 nmol/l, p=0.0003). CONCLUSIONS/INTERPRETATION: Assessment of islet antibodies is necessary for the aetiological classification of diabetic patients. HLA-DQB1 genotyping does not improve the classification in patients with islet antibodies. However, in patients without islet antibodies, HLA-DQB1 genotyping together with C-peptide measurement may be of value in differentiating between idiopathic type 1 diabetes and type 2 diabetes.

Adolescent↗
PubMed1998

Hepatitis C virus genotypes and the influence of the induction of immunosuppression with anti-thymocyte globulin (ATG) on chronic hepatitis in renal graft recipients.

Hepatitis C virus (HCV) exhibits a dramatic genetic variability and several mechanisms of immunological response are unable to control hepatic and extrahepatic replication. Genotype 1 b is associated with more severe clinical manifestations and is less responsive to interferon. In addition, we have reported an increase of HCV RNA viral load after renal transplantation. Anti-thymocyte globulin (ATG) is supposed to increase viral replication and liver dysfunction in chronically infected renal graft recipients. We evaluated the genotype profile in HCV+ patients of our Renal Transplant Unit and studied the effects of ATG, as part of the induction of immunosuppression, on viral load and liver enzymes abnormalities. From 726 renal graft recipients, 104 patients, with a mean follow up of 3.9 +/- 2.9 years, were anti-HCV+ by ELISA II. HCV RNA was measured by quantitative PCR. We correlated the viral load and biochemical liver parameters with genotype, exposure to ATG as induction therapy, early acute rejection episode and the duration of infection. Of the 81 patients tested, 72% were viraemic and genotype 1 b was the predominant viral strain (66%). The majority of these patients (65%) were coinfected by two or more strains. There was no correlation between HCV RNA blood levels and liver enzymes. We did not find higher viral load with genotype 1 b infection (68 +/- 88 mEq/ml vs 75.8 +/- 123 mEq/ml in the others) nor with ATG induction therapy (43.5 +/- 71.3 mEq/ml vs 64.1 +/- 110.5 mEq/ml). Early acute rejection and longer follow up were not associated with higher levels of HCV RNA. The biochemical liver profile showed no relationship with the variables studied. We concluded that genotype 1 b is the predominant strain in our HCV+ population and there is a great prevalence of coinfection with several genotypes. Our results did not confirm a deleterious effect of the use of ATG as induction therapy in these HCV-infected patients. Prospective randomised studies with liver biopsy evaluation are needed to answer more fully the remaining questions about the best immunosuppressive therapy in renal graft recipients with chronic HCV infection.

Genotype↗
PubMed2001

Prediction of osteoporotic fractures by bone densitometry and COLIA1 genotyping: a prospective, population-based study in men and women.

Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mineral density and increased fracture risk. Although the genetic basis of osteoporosis is incompletely understood, previous studies have identified a polymorphism affecting an Sp1 binding site in the COLIA1 gene that predicts bone mineral density and osteoporotic fractures in several populations. Here we investigated the role of COLIA1 genotyping and bone densitometry in the prediction of osteoporotic fractures in a prospective, population-based study of men (n = 156) and women (n = 185) who were followed up for a mean (+/- SEM) of 4.88+/-0.03 years. There was no significant difference in bone density, rate of bone loss, body weight, height, or years since menopause between the genotype groups but women with the 'ss' genotype were significantly older than the other genotype groups (p = 0.03). Thirty-nine individuals sustained 54 fractures during follow-up and these predominantly occurred in women (45 fractures in 30 individuals). Fractures were significantly more common in females who carried the COLIA1 's' allele (p = 0.001), although there was no significant association between COLIA1 genotype and the occurrence of fractures in men. Logistic regression analysis showed that carriage of the COLIA1 's' allele was an independent predictor of fracture in women with an odds ratio (OR) [95% CI] of 2.59 [1.23-5.45], along with spine bone mineral density (OR = 1.57 [1.04-2.37] per Z-score unit) and body weight (OR = 1.05 [1.01-1.10] per kilogram). Moreover, bone densitometry and COLIA1 genotyping interacted significantly to enhance fracture prediction in women (p = 0.01), such that the incidence of fractures was 45 times higher in those with low BMD who carried the 's' allele (24.3 fractures/100 patient-years) compared with those with high BMD who were 'SS' homozygotes (0.54 fracture/100 patient-years). We conclude that in our population, COLIA1 genotyping predicts fractures independently of bone mass and interacts with bone densitometry to help identify women who are at high and low risk of sustaining osteoporotic fractures.

Absorptiometry, Photon↗
PubMed2002

Association between head and neck cancer and microsomal epoxide hydrolase genotypes.

Tobacco-associated carcinogens are catalyzed by microsomal epoxide hydrolase (mEH). Combinations of the Y113H and H139R polymorphic EPHX1 variants have been assumed to alter the enzyme activity and thus the risk of squamous cell head and neck cancer (SCCHN). Based on in vitro data, a putative low, medium and high mEH activity has been associated with combinations of these genotypes, and the respective activity categories have been frequently used in the estimation of risks for smoking-related cancers. We investigated the SCCHN risk for EPHX1 genotypes among 280 cases and 289 controls. We could not detect main effects of the EPHX1 genotypes, but a smaller risk of the 139HR genotype in smokers (odds ratio, OR, 0.57; 95% confidence interval, CI, 0.34-0.95). We could not confirm an increase of the SCCHN risk for genotype combinations according to a putative medium and high enzyme activity (OR 1.28, 95% CI 0.84-1.96; OR 0.98, 95% CI 0.58-1.64, respectively), but a significant heterogeneity of the estimated risks for the singular genotypes within these categories among smokers ( P=0.02). Further, p53 mutations among smoking cases were less frequent in the group with a putative high enzyme activity, although insignificant due to small numbers (OR 0.54, 95% CI 0.13-2.17). This supports uncertainties in categorizing genotypes with respect to limited enzyme activity data, especially when taken from in vitro experiments.

Carcinoma, Squamous Cell↗
PubMed1997

The GST T1 and CYP2E1 genotypes are possible factors causing vinyl chloride induced abnormal liver function.

Vinyl chloride monomer (VCM) is hepatotoxic as well as carcinogenic in humans. There are reports that exposure to VCM seems to induce abnormal liver function, liver fibrosis, cirrhosis, portal hypertension, and angiosarcoma of the liver. In vivo, VCM is metabolized by cytochrome P450 2E1 (CYP2E1) to form the electrophilic metabolites, chloroethylene oxide (CEO) and chloroacetaldehyde (CAA), which may either cause cell damage or be further metabolized and detoxified by glutathione S-transferases (GSTs). This study investigated whether or not the genotypes CYP2E1, glutathione S-transferase theta (GST T1) and mu (GST M1) correlated with abnormal liver function found in vinyl chloride exposed workers. For this study, 251 workers from five polyvinyl chloride plants were enrolled. The workers were classified into two exposure groups (high and low) and the degree of exposure was determined based on their job titles and airborne VCM concentration. The activity of serum alanine aminotransferase (ALT) was used as the parameter of liver function. The genotypes CYP2E1, GST T1 and GST M1 were determined by polymerase chain reaction and restriction fragment length polymorphism on peripheral white blood cell DNA. Other potential risk factors were also ascertained and the confounding effect was adjusted accordingly. Stratified analyses were used to explore the correlation between the alteration of liver function and the genotypes CYP2E1, GST T1 and GST M1 among the workers exposed to different levels of VCM. The following results were obtained (1) at low VCM exposure, the odds ratio (OR) of positive GST T1 on abnormal ALT was 3.8 (95% CI 1.2-14.5) but the CYP2E1 genotype was not associated with abnormal ALT. (2) At high VCM exposure, a c2c2 CYP2E1 genotype was associated with increased OR on abnormal ALT (OR 5.4, 95% CI 0.7-35.1) and positive GST T1 was significantly associated with decreased OR on abnormal ALT (OR 0.3, 95% CI 0.1-0.9). (3) Multiple linear and logistic regression also showed strong interactions of the VCM exposure to CYP2E1 as well as to the GST T1 genotype. These observations suggest that the two genotypes, CYP2E1 and GST T1, may play important roles in the biotransformation of VCM, the effect of which leads to liver damage.

Adult↗
PubMed2002

CYP2D6 extensive, intermediate, and poor phenotypes and genotypes in a Polish population.

OBJECTIVE: This study investigated the distribution of the CYP2D6 genotypes and phenotypes in a Polish population and compared the concordance of the two methods. METHODS: Six hundred unrelated healthy individuals from southwestern Poland were studied. The CYP2D6 phenotype was analyzed in 300 individuals using sparteine as a model drug. The CYP2D6 genotype was analyzed in 300 individuals by polymerase chain reaction amplification and restriction fragment length polymorphism techniques for the CYP2D6*1, CYP2D6*3, and CYP2D6*4 alleles. Additionally, in 60 randomly selected healthy individuals both the CYP2D6 phenotype and genotype was assessed to determine accordance between the methods. RESULTS: Of 300 participants in the study 25 (8.3%) were classified as poor metabolizers, 44 (14.7%) as intermediate metabolizers, and 231 (77%) as extensive metabolizers of sparteine. The frequency of CYP2D6*1, CYP2D6*3, and CYP2D6*4 alleles among the genotyped 300 persons was 75.7%, 1.3%, and 23.0%, respectively. The frequency of CYP2D6 deficient genotypes in a Polish population (8.0%) was similar to phenotyping results. The comparison of phenotype and genotype in 60 randomly selected individuals showed a good concordance of the obtained results. CONCLUSIONS. The frequencies of poor metabolizers for CYP2D6 phenotype (8.3%) and genotype (8.0%) in a Polish population from the southwestern region are in concordance and compare well with most results of poor oxidation metabolizers in other white populations.

Adolescent↗
PubMed2006

The influence of various genotypes on the metabolic activity of NAT2 in a Chinese population.

AIM: To determine the phenotype and genotype of NAT2 in a Chinese population and study the influence of various NAT2 genotypes on the NAT2 activity. METHODS: A reverse dot blot method was used to detect the genotype of NAT2 in 120 healthy Chinese subjects. All subjects were given a single dose of 500 mg sulphadimidine (SM(2)). The plasma concentration of SM(2) and acetyl-SM(2) (AcSM(2)) 6 h after administration was determined. Molar metabolic ratio (MR) was calculated by the ratio of AcSM(2) to AcSM(2)+SM(2). RESULTS: Totals of 53 (44.2%), 47 (39.2%) and 20 (16.7%) subjects were homozygotes for wild type (wt/wt), heterozygotes for mutant (m/wt) and homozygotes for mutant (m/m), respectively. The MR of 120 subjects was 0.714+/-0.237. Twenty subjects (16.7%) were classified as poor metabolizers. All subjects in the m/m group were poor metabolizers. The MRs of the wt/wt, m/wt and m/m groups were 0.886+/-0.060, 0.719+/-0.089 and 0.246+/-0.105 (P<0.001), respectively. There was a significant difference between different NAT2 m/wt genotypes (P<0.001) and m/m genotypes (P<0.001). MR correlated well with NAT2 genotypes (r=0.947). CONCLUSION: Various NAT2 genotypes have a significant impact on the metabolic activity of NAT2 in Chinese people.

Adult↗
PubMed2006

CYP2E1 genotype and isoniazid-induced hepatotoxicity in patients treated for latent tuberculosis.

OBJECTIVE: To determine whether pharmacogenetic tests such as N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1) genotyping are useful in identifying patients prone to antituberculosis drug-induced hepatotoxicity in a cosmopolite population. METHODS: In a prospective study we genotyped 89 patients treated with isoniazid (INH) for latent tuberculosis. INH-induced hepatitis (INH-H) or elevated liver enzymes including hepatitis (INH-ELE) was diagnosed based on the clinical diagnostic scale (CDS) designed for routine clinical practice. NAT2 genotypes were assessed by fluorescence resonance energy transfer probe after PCR analysis, and CYP2E1 genotypes were determined by PCR with restriction fragment length polymorphism analysis. RESULTS: Twenty-six patients (29%) had INH-ELE, while eight (9%) presented with INH-H leading to INH treatment interruption. We report no significant influence of NAT2 polymorphism, but we did find a significant association between the CYP2E1 *1A/*1A genotype and INH-ELE (OR: 3.4; 95% CI:1.1-12; p = 0.02) and a non significant trend for INH-H (OR: 5.9; 95% CI: 0.69-270; p = 0.13) compared with other CYP2E1 genotypes. This test for predicting INH-ELE had a positive predictive value (PPV) of 39% (95% CI: 26-54%) and a negative predictive value (NPV) of 84% (95% CI: 69-94%). CONCLUSION: The genotyping of CYP2E1 polymorphisms may be a useful predictive tool in the common setting of a highly heterogeneous population for predicting isoniazid-induced hepatic toxicity. Larger prospective randomized trials are needed to confirm these results.

Adolescent↗
PubMed2000

Correlation between acetylation phenotype and genotype in Chinese women.

OBJECTIVE: The acetylation polymorphism is a common inherited variation in human drug and carcinogen metabolism. Because N-acetyltransferase (NAT2) is important for the detoxification and/or bioactivation of drugs and carcinogens, this polymorphism has important implications in therapeutics and cancer susceptibility. A high correlation between acetylation phenotype and genotype has been demonstrated in several studies. However, no such data exist for Chinese females. The aim of the present study was to compare acetylation phenotype with NAT2 genotype in a population of primarily non-smoking Chinese females. METHODS: In the present study, the correlation between N-acetyltransferase activity and NAT2 genotype was evaluated in 103 unrelated Chinese female controls derived from a hospital-based case-control study of lung cancer in Singapore. Acetylation phenotype and genotype were respectively determined using caffeine and an allele-specific polymerase chain reaction (PCR). RESULTS: The proportions of rapid and slow phenotypes were 78% and 22%, respectively, while the distribution of rapid (heterozygotes and homozygotes combined) and slow acetylator genotypes was 76% and 24%, respectively. The distribution of the various NAT2 genotypes did not differ significantly (chi2 = 1.45, P > 0.05) from that predicted by the Hardy-Weinberg Law. All slow acetylators were accurately predicted (100%), whereas 2 of 80 rapid acetylators were erroneously predicted as slow (2.5%). The overall prediction rate of the PCR-based test for the acetylation phenotype was at 98.1% in our Chinese population. CONCLUSION: Our results suggest that genotyping with PCR may well become the preferred method for the determination of acetylation polymorphism in epidemiological studies in this Asian population.

Acetylation↗
PubMed1999

CYP2C19 genotypes and omeprazole metabolism after single and repeated dosing when combined with clarithromycin.

OBJECTIVES: Omeprazole is metabolized mainly by CYP2C19 which has two major mutations (CYP2C19*2 in exon5 and CYP2C19*3 in exon4) associated with the poor metabolizer (PM) phenotype. The aim of this study was to examine the relationship between genetic polymorphism of CYP2C19 and metabolism of omeprazole administrated as a single dose or as repeated-doses, which were in both cases co-administered with clarithromycin. METHODS: Twelve healthy Japanese subjects were typed for CYP2C19 polymorphism. In the single-dose study, plasma levels of omeprazole and its metabolites were measured for 24 h after administration of 20 mg omeprazole and 400 mg clarithromycin to six healthy Japanese subjects. In the repeated-dose study, plasma levels of omeprazole and its metabolites were measured after repeated oral administration of 20 mg omeprazole and 400 mg clarithromycin twice daily for 6 days and then after 20 mg omeprazole and 400 mg clarithromycin once on the 7th day to the other 6 healthy Japanese subjects. RESULTS: In the single-dose study, the areas under the plasma concentration-versus-time curve (AUCs) of omeprazole of homozygotes for the wild-type allele (*1/*1 n = 2), heterozygotes (n = 3) for the CYP2C19*2 (*1/ *2) or for the CYP2C19*3 (*1/*3) and heterozygote (n = 1) for the two defects (*2/*3) were on average 450, 1007 and 6710 ng x h(-1) x ml(-1), respectively. The ratios of AUCs of omeprazole/5-hydroxyomeprazole for *1/*1, *1/*2 or *1/*3 and *2/*3 were 1, 2 and 30, respectively. In the repeated-dose study, the AUCs of omeprazole for * 1/ *1, *1/*2 or *1/*3 and *2/*3 were 4041 (n = 2), 3149 (n = 3) and 6684 (n = 1) ng x h(-1) x ml(-1), respectively. The ratios of AUCs of omeprazole/5-hydroxyomeprazole for *1/*1, * 1/*2 or * 1/*3 and *2/*3 were7, 11 and 30, respectively. In the repeated-dose study, the AUC of omeprazole of * 1/*1 genotypes was nine-fold higher, that of *1/*2 and *1/*3 genotypes was three-fold higher, and the Cmax value of omeprazole was three-fold higher compared with subjects with the same genotype in the single-dose study. However, there were few differences in the AUC and Cmax of omeprazole between the *2/*3 genotype in the single-dose study and the homozygote for the CYP2C19*2 (*2/*2) in the repeated-dose study. CONCLUSION: Subjects with *1/*1, *1/*2 and *1/*3 genotypes in the repeated-dose study had lower CYP2C19 activity than subjects of the same genotype in the single-dose study. The difference in omeprazole metabolism between subjects with different genotypes observed on day 1 seemed to disappear after 7 days of repeated-dose administration.

Adult↗
PubMed2005

The HLA-G genotype is associated with IL-10 levels in activated PBMCs.

Human leukocyte antigen (HLA)-G is an MHC class Ib molecule that is expressed at the feto-maternal interface during pregnancy. However, recent results have also shown that it may have important functions as an immuno-modulatory factor in adult life. Differences in the pattern of alternative splicing and in the stability of HLA-G mRNA transcripts have been associated with HLA-G polymorphisms, especially a 14 bp deletion/insertion polymorphism in the 3' untranslated region of the HLA-G gene. We have investigated the secretion of HLA-G5/soluble HLA-G1 and interleukin-10 (IL-10) in lipopolysaccharide (LPS)-activated peripheral blood mononuclear lymphocytes (PBMCs) in relation to the HLA-G 14 bp genotype. No HLA-G5/sHLA-G1 could be detected in the non-activated control PBMC culture media, and there were no significant differences among the three HLA-G 14 bp genotypes regarding IL-10 concentrations. In LPS-activated PBMC cultures, no significant differences among the three HLA-G 14 bp genotypes regarding HLA-G5/sHLA-G1 concentrations were observed. However, this was in contrast to the IL-10 levels (P=0.0004, Kruskal-Wallis test). The +14/+14 bp PBMC samples expressed higher levels of IL-10 when compared to the -14/+14 bp genotype and the -14/-14 bp genotype. Interestingly, the IL-10 G/G polymorphism at position -1082 was more frequent in the +14/+14 bp genotype (P=0.024, chi2 test). These results support an autocrine loop between HLA-G5/sHLA-G1 and IL-10 expression in activated PBMCs, which may result in higher IL-10 levels in +14/+14 bp HLA-G genotypes.

3' Untranslated Regions↗
PubMed2002

Distribution of Lewis (FUT3)genotype and allele: frequencies in a biethnic United States population.

The objective of the study was to examine the prevalence and distribution of four major single nucleotide polymorphisms (SNPs) (T59G, T1067G, T202C, and C314T) of the Lewis ( FUT3)gene in a biethnic United States population. This population-based cross-sectional study was based on data from the Atherosclerosis Risk in Communities (ARIC) Study, which included 761 males and females aged 45-64 years, who had no known/detected clinical atherosclerotic disease (577 Caucasians, 184 African Americans). The main outcome measures were prevalence of the Lewis genotype and allele frequencies for four SNPs of the FUT3gene. The most common genotype was the "wild type" at all four nucleotide positions ( WWWW), which was found to be present in 46.9% of ARIC participants. At least one mutant allele was detected in 51.7% of Caucasians, and 56.7% of African Americans ( P=0.59). The frequencies of mutant alleles ranged from 6.3% to 18.4% at the four FUT3gene sites examined. The distribution of the Lewis genotype and allele frequencies differed significantly by ethnicity at sites 59, 202, and 314. The prevalence of the Lewis genotype suggesting a lack of alpha(1,3/1,4) fucosyltransferase activity was 11.6% in Caucasians and 9.9% in African Americans ( P=0.67). Four specific SNPs of the Lewis genotype are common in the population at large. However, these four SNPs seem to fail to explain the majority of Lewis-negative phenotype in African Americans, given that Lewis-negative genotype prevalence was about one-third of what was expected. Use of rapid DNA sequencing and simultaneous Lewis phenotype determination could avoid the problems associated with haplotype determination and Lewis genotype grouping. Further studies testing SNPs of the Lewisgene are warranted, in particular among African Americans.

Age Factors↗
PubMed1996

Preferential RNA editing at specific sites within transcripts of two plant mitochondrial genes does not depend on transcriptional context or nuclear genotype.

Transcripts of most plant mitochondrial protein-coding genes exhibit C-to-U RNA editing events. In Petunia, two co-transcribed genes, nad3 and rps12, exhibit transcripts which are not fully edited at all potential editing sites. We investigated the nad3/rps12 transcript population in four different genotypes. In one pair of genotypes, the nuclear genome is identical but the nad3/rps12 genes are in different transcriptional contexts. Both the nad3/ rps12 genes and the plant mitochondrial genomes are identical in a second pair of genotypes, but the nuclear background is derived from two different Petunia species. We found that the overall extent of editing varied greatly between genotypes and is affected by nuclear genotype but not by the global transcriptional context. Local sequence context around a particular site does affect editing frequency. In all genotypes, certain sites exhibit high editing frequency, but these sites do not share obvious primary sequence characteristics. In all genotypes examined, editing sites which do not affect the encoded amino acid are less frequently edited than sites which alter codons to non-synonymous forms. All these data indicate that an unidentified property of the sequences immediately surrounding a cytosine affect its selection as a target in the editing process.

Amino Acid Sequence↗
PubMed2003

Infectivity of Cryptosporidium parvum genotype I in conventionally reared piglets and lambs.

Parasites of the genus Cryptosporidium are intracellular parasites that occur throughout the animal kingdom and have been reported in many species of mammals, including human. Most infections in humans are caused by two C. parvum genotypes, genotype I and genotype II; these are the human and the bovine (zoonotic) genotypes, respectively. Successful experimental infection of Cryptosporidium parvum genotype I "human genotype" is described in four conventionally reared piglets and in a lamb. The inoculum was originally obtained from two diarrheic children, and the Cryptosporidium genotypes were determined by PCR and rDNA sequencing. The infective dose was between 10(6) and 2 x 10(6) oocysts. No clinical signs were observed in the infected animals, except in a piglet that showed watery diarrhea. The oocyst shedding period in positive animals ranged between 4 and 10 days. Histopathologic examination of the gastrointestinal tract of two positive piglets revealed shortening of the villi and denudation of the villous tips of the jejunum. In one piglet, the colon mucosa revealed numerous Cryptosporidium oocysts. The storage time of the inocula (< or =3 weeks in PBS at 4 degrees C) and the age of the animal (newborn) were important for the successful induction of infection.

Animals↗
PubMed1996

Are men carrying the apolipoprotein epsilon 4- or epsilon 2 allele less fertile than epsilon 3 epsilon 3 genotypes?

The epsilon 3 allele in the human gene coding for apolipoprotein E (apoE) is the most common worldwide, but epsilon 4 is probably the ancestral allele. Since apoE is involved in many important biological processes, selection forces could have favoured epsilon 3. We hypothesized that apoE genotypes may affect reproductive efficiency, and we therefore compared the distributions of 40-year-old married men with known genotypes by the numbers of their biological children. The distributions were statistically significantly different (P = 0.0026). On average, men with the epsilon 3 epsilon 3 genotype (n = 212) had 1.93 children, men with the epsilon 3 epsilon 4 or epsilon 4 epsilon 4 genotype (n = 105) had 1.50, and men with the epsilon 3 epsilon 2 or epsilon 2 epsilon 2 genotypes (n = 53) had 1.66 children. Of the men in the three groups, 6%, 26% and 19%, respectively, reported being childless. These findings are unlikely to be due to gross error in the reported prevalence of childlessness, differences in socioeconomic status or other likely sources of bias. They are compatible with higher fertility in men with the epsilon 3 epsilon 3 genotype than in those with the other common apoE genotypes.

Adult↗
PubMed1998

Change of bone mass in postmenopausal Caucasian women with and without hormone replacement therapy is associated with vitamin D receptor and estrogen receptor genotypes.

Our purpose is to assess whether genotypes of the vitamin D receptor (VDR) and estrogen receptor (ER) and their interaction influence changes in bone mass in postmenopausal Caucasian women with and without hormone replacement therapy (HRT). A population of 108 US Mid-West women who participated in a study of low-dose continuous estrogen/progestin was genotyped at the VDR BsmI site and the ER XbaI and PvuII sites. Adequate vitamin D and calcium nutritional intakes were assured in all the study subjects. For the 3.5-year duration of the study, we analyzed changes in bone mineral density (BMD) at the spine, femoral neck, distal radius, and the total body (total body bone mineral content, tbBMC). We adjusted for confounding factors, such as age and weight, in the analysis. We found that VDR and/or ER genotypes and/or their interaction generally had significant effects on the changes in the bone mass measurements in both the placebo and HRT groups. When a significant gene-by-gene interaction exists between VDR and ER genotypes, failure to account for them in analyses may yield nonsignificant results, even if significant genotypic effects exist. The amount of variation in changes in bone mass measurements explained by the total genotypic effects of the VDR and ER loci varies from approximately 1.0% (for the tbBMC changes in combined placebo and HRT groups) to approximately 18.7% (for the spine BMD changes in the HRT group). These results suggest that individual genotypes are important factors in determining changes in bone mass in the elderly with and without HRT and thus may need to be considered with respect to the treatment to preserve bone mass in elderly Caucasian women.

Aged↗
PubMed1998

Usefulness of hepatitis C virus RNA counts by second generation HCV bDNA-probe in chronic hepatitis C based on the HCV genotype.

Detection of hepatitis C virus (HCV) RNA by a second generation (ver 2) HCV bDNA-probe method (bDNA-probe) was compared with detection by the first generation (ver 1) assay. The two assays were performed simultaneously with the same serum samples of HCV genotypes 1b, 2a, 2b, 3a, and 3b. The positive rates with ver 1 were 82% for HCV genotype 1b (type 1b), 57.6% for HCV genotype 2a (type 2a), 75.0% for HCV genotype 2b (type 2b), 55.6% for HCV genotype 3a (type 3a), and 93.8% for HCV genotype 3b (type 3b). The positive rates with ver 2 were 95.0% for type 1b, 93.9% for type 2a, 83.3% for type 2b, 100% for type 3a, and 93.8% for type 3b. With Fisher's exact test, the detection rate for type 2a was significantly higher (P = 0.001) with ver 2 than with ver 1. We obtained regression lines using the HCV counts measured by bDNA-probe on the y axis and the HCV counts obtained by an HCV reverse transcriptase (RT)-competitive polymerase chain reaction method (competitive PCR) on the x axis. The gradients for types 1b, 2a, and 3b were greater with ver 2 compared to ver 1. The gradients for types 2a and 3b were the highest: for type 2a, y = 0.135x + 0.6 with ver 1 and y = 0.248x + 0.1 with ver 2; for type 3b, y = 0.366x + 0.1 with ver 1 and y = 0.727x + 0.3 for ver 2. In addition, HCV-RNA counts for all the genotypes tested in this study were significantly higher with ver 2 than with ver 1. Hence, we conclude that ver 2 of the bDNA-probe measures HCV-RNA counts closer to those obtained with competitive PCR than the ver 1 assay.

DNA Probes↗
PubMed2005

Serotonin transporter promoter polymorphism genotype is associated with temperament, personality traits and illegal drugs use among adolescents.

Serotonin transporter promoter polymorphism (5-HTTLPR) genotype was previously found associated with substance use disorders, particularly in the subjects with comorbid antisocial behavior, and with temperament and personality traits at risk for substance abuse. Aim of the present study was to evaluate the possible association between 5-HTTLPR genotype and the availability to experiment illegal drugs among adolescents, in relationship with psychological characteristics. 216 caucasian high school students (aged 14-19 ys), 125 abstinent subjects, who have never experimented psychotropic drugs, and 91 experimenters of illegal drugs have been genotyped. Aggressiveness levels and temperamental traits were measured in both abstinent subjects and experimenters utilizing respectively Buss-Durkee-Hostility-Inventory (BDHI) and Cloninger Three-dimensional Personality Questionnaire (TPQ). Data about school performance have been also collected. The short-short (SS) genotype frequency was significantly higher among experimenters compared with abstinent subjects (p = 0.001). The odds ratio for the SS genotype vs the long-long (LL) genotype frequency was 4.67, 95% Cl (1.97-11.04), when experimenters were compared with abstinent students. The SS genotype frequency was significantly higher among aggressive/novelty seeker (NS) experimenters with poor school achievements, compared with drugs experimenters without aggressiveness and school failure (p = 0.02). When evaluated on the entire sample, BDHI mean total scores, NS scores at TPQ and school failure frequency were significantly higher in SS individuals, in comparison with LL subjects. Our data suggest that a decreased expression of the gene encoding the 5-HTT transporter, due to "S" promoter polymorphism, may be associated with an increased availability to experiment illegal drugs among adolescents, particularly in the subjects with more consistent aggressiveness, NS temperament and learning disabilities.

Adolescent↗