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PubMed1995

Selection of more pathogenic hepatitis C virus genotype II during long-term follow-up of interferon-treated patients.

The behavior of hepatitis C virus (HCV) infection with regards to type and number of HCV genotypes (tested with genotype-specific nested polymerase chain reaction) was evaluated in 60 patients with anti-HCV-positive chronic active hepatitis without cirrhosis [17 untreated and 43 subjects undergoing single or repeat courses of interferon (IFN) therapy] during a mean follow-up period of 76 +/- 18 months. In untreated patients (2 genotype I, 6 genotype II, 9 mixed infections) 4 out of 9 mixed infections selected for genotype II at the end of follow-up. Of the 43 treated patients 10 were long-term responders with histological remission, 6 were short-term responders, and 22 did not respond. Fifteen of the latter patients received another course of IFN therapy, and only 3 patients responded. Eight of the 10 responders had infection with a single genotype (4 gt I, 3 gt II, 3 gt III). After IFN therapy, all but 2 patients cleared the HCV infection. The responders to the second IFN course (1 gt I, 1 gt II, 1 gt III) remained viremic. Of the short-term responders, 2/6 patients had genotype II and 4 had a mixed infection (3 gt II +/- I and 1 gt II +/- III); gt III became prevalent in the latter in all but one patient. Of the nonresponders 18/24 had more than one genotype, 5 were genotype II at baseline and one had genotype I. At the end of the follow-up period 15/18 with mixed infection had selected for gt II (P < 0.01 vs. untreated patient).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Preparation of herpes simplex virus type 1 genomic markers to differentiate strains of predominant genotypes.

Analyses of restriction fragment length polymorphism (RFLP) of herpes simplex virus type 1 (HSV-1) isolated in Japan using restriction endonucleases recognizing 6-base pairs revealed the presence of two predominant genotypes of F1 and F35. Therefore, the possibility that the two predominant genotypes may differ in clinical manifestations had to be considered. To address the question of whether differences in genotype would reflect clinical presentations of HSV-1 infection, RFLP markers to differentiate strains of predominant genotypes are required. In the present work, DNAs of 66 HSV-1 strains were analyzed, using restriction endonucleases recognizing 4-base pairs of HaeIII, HhaI, and MboI, the objective being to detect a large number of RFLP. The relationship between the 154 identified RFLPs and each predominant genotype of F1 and F35 was traced. RFLPs closely related to each predominant genotype were manifested, as the first case of a set of RFLPs diagnostic for the predominant genotypes. These diagnostic RFLPs will facilitate knowledge on association of predominant genotypes with clinical manifestations by efficiently identifying HSV-1 strains of a genotype, and, in addition, HSV-1 strains of a predominant genotype derived from a common ancestor.

Animals↗
PubMed1994

Hepatitis C virus genotypes are not responsible for development of serious liver disease.

Although hepatitis C virus (HCV) is known to have at least four kinds of genotypes, no clear relationship has yet been established between the genotype and the severity of liver disease. Therefore, we determined HCV genotypes in sera of 251 Japanese patients with type C chronic liver disease, using polymerase chain reactions with six independent primers. One set of primers and a probe derived from 5'-noncoding region of HC-J1 was supposed to detect all four genotypes, while the other five were devised to detect each of the genotypes. Among the patients, the major genotype was type II (69%) and the second most common was type III (18%). Type IV was found in 7%, while none had type I genotype. There was no significant difference in the distribution of any genotype among different stages of liver disease, although the ratio of type II to type III tended to be higher in the group of cirrhosis and hepatocellular carcinoma than in the chronic hepatitis group (5.5 vs 3.0). The amounts of HCV RNA were significantly greater in patients with type II (P < 0.001) compared with those with types III and IV. However, HCV concentrations of each genotype were not associated with the disease status. These results suggest that HCV genotypes are unlikely to be responsible for the development of more serious liver disease.

Adult↗
PubMedDate not supplied

Molecular epidemiology of hepatitis B viral serotypes and genotypes in taiwan.

Subtypes of hepatitis B virus (HBV) have specific geographic distributions and can serve as epidemiological markers. The relationship of HBV serotypes and genotypes in Taiwan and their correlation with the domiciles of origin in 122 patients with chronic HBV infection were investigated. The serotype of HBV was determined by comparing the surface gene encoding amino acids 22-148 of the major surface protein with published sequences. Genotyping of HBV was performed by polymerase chain reaction-restriction fragment length polymorphism. Serotype adw accounted for 70% (85/122) of all HBVs, with the remaining belonging to serotype adr. All adr HBVs were genotype C, regardless of the patient's domicile. Of the 85 adw HBVs, 69 (81%) were genotype B, 10 (12%) were genotype C, 5 (6%) were genotype F and only 1 (1%) was genotype A. In the 31 patients originating from mainland China, the prevalence of adr/genotype C was higher than in the 91 Taiwanese patients (15/31 vs. 22/91; p < 0.05). The distribution of the HBV serotypes and genotypes was not significantly different between 17 patients born in Taiwan (6 adw/genotype B, 2 adw/genotype C, 1 adw/genotype F and 8 adr/genotype C) and 14 patients born in mainland China (5 adw/genotype B, 2 adw/genotype C and 7 adr/genotype C). Our results indicate that in Taiwan, most HBVs of serotype adw are genotype B, and all HBVs of serotype adr are genotype C. Patients with origins in mainland China have a higher proportion of serotype adr/genotype C infection.

Adult↗
PubMed2002

Relationship between glucocorticoid-induced osteoporosis and vitamin D receptor genotypes.

By means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay, the association between vitamin D receptor (VDR) genotypes and bone mineral density (BMD) in the patients receiving long-term glucocorticoid therapy was studied. The clinical data and blood of 71 patients with rheumatosis who received long-term glucocorticoid therapy were collected. BMD was measured by dual-energy X-ray absorptimometry. VDR gene fragment (about 185 bp) was amplified by PCR from the extracted genomic DNA, then digested with restriction endonuclease Bsm I. The genotypes were evaluated based on the fragment length following endonuclease digestion and the association between genotypes and BMD or Z-score values was analyzed. Among the 71 cases, the detected genotypes were Bb and bb with the distribution frequency being 11.3% and 88.7% respectively. The distribution frequency of the alleles was in agreement with the Hardy-Weinberg equilibrium. There was no significant difference between the two genotypes in age, gender, body mass index (BMI), disease duration, disease types, time of glucocorticoid administration and cumulative dosage (P > 0.05). Osteoporosis rate of the patients with Bb or bb genotype was 37.5% and 33.3% respectively, with the difference being not significant (chi 2 = 0.05, P = 0.8). The BMD and Z-score values at lumbar spine and femur in two genotypes were not similar, but the difference had no significant (P > 0.05). The distribution frequency of bb type of VDR genotypes in Han populations of China was more prevalent, followed by Bb and bb types in turn. In the patients receiving long-term glucocorticoid therapy, there was no significant difference in BMD between Bb and bb genotypes. The data suggest that the VDR genotypes may not be means of identifying patients at greater risk of glucocorticoid-induced osteoporosis, which await to be further confirmed by a large sample size.

Adolescent↗
PubMed2006

Endogenous histamine and cortisol levels in subjects with different histamine N-methyltransferase C314T genotypes : a pilot study.

BACKGROUND: Histamine N-methyltransferase (HNMT) catalyzes the methylation of histamine and plays an important role in histamine biotransformation in bronchial epithelium. Enzymatic activity of HNMT has been shown to be regulated by genetic factors, including polymorphisms in the HNMT gene. In this pilot study we determined endogenous levels of histamine and cortisol in plasma and whole blood samples from subjects with different genotypes for the HNMT C314T polymorphism, and investigated whether these parameters differed between individuals with the HNMT CC genotype and those with the CT genotype. METHODS: Blood samples were collected from 48 unrelated volunteers (36 males, 12 females), aged 21-40 years, who participated in the study. PCR-restriction fragment length polymorphism analysis was used to determine HNMT C314T genotypes. Erythrocyte HNMT activity was determined as well as plasma and whole blood levels of histamine and cortisol. Two-group comparisons of the various parameters were analyzed by Blocked Wilcoxon test and Wilcoxon Rank Sum test as appropriate. RESULTS: Thirty-seven subjects (24 Caucasians, three African Americans, one Middle Eastern, five Indians, three Chinese, and one Filipino) were found to have the homozygous CC genotype. Ten subjects (eight Caucasians, one Middle Eastern, and one Chinese) were heterozygous and one individual (Pakistani) was homozygous for the variant 314T allele. The frequency of HNMT CT heterozygotes in the small Caucasian cohort was 0.125. Median enzyme activity was significantly lower in subjects with the heterozygous CT genotype than in those with the homozygous CC genotype (485 vs 631 U/mL of red blood cells; p=0.023). A broad range of histamine levels in plasma and whole blood was observed for all subjects. Whereas the median plasma histamine level was found to be higher in heterozygotes for the wild-type 314C allele than homozygotes (3.32 vs 2.30 nmol/L; p=0.021), there was no difference between the two groups in histamine levels in whole blood. Cortisol levels were similar between individuals with the homozygous CC genotype and those with the heterozygous CT genotype. CONCLUSION: Wide variability of plasma and whole-blood histamine levels was observed in subjects with different HNMT C314T genotypes. Endogenous levels of histamine are likely to be affected by various genes and polymorphisms.

Adult↗
PubMed2006

Vitamin D receptor genotype and risk of osteoporotic hip fracture in elderly women of Utah: an effect modified by parity.

INTRODUCTION: The associations between vitamin D receptor (VDR) Bsm I and Fok I genotypes, parity, and risk of osteoporotic hip fracture were evaluated in a statewide population-based case-control study in Utah. METHODS: Women age 50-89 years with hip fracture (n=882) were ascertained via surveillance of 18 Utah hospitals from 1997 to 2001. Age-matched controls were randomly selected (n=897). Participants were interviewed in their homes, and blood samples were collected for genotyping. RESULTS: In logistic regression analyses that controlled for multiple confounders, Bsm I VDR genotype but not Fok I genotype was associated with risk of osteoporotic hip fracture (OR bb vs. BB genotype: 0.68; 95% CI: 0.50, 0.95). In similar analyses, no overall association was observed between parity status and risk of osteoporotic hip fracture. However, the effect of VDR genotype was modified by parity status. Among nulliparous women (n=140), Bsm I genotype was not associated with risk of hip fracture (OR bb vs. BB: 0.82; 95% CI: 0.28, 2.4); among primiparous women (n=133), bb genotype was associated with increased risk of hip fracture (OR bb vs. BB: 3.30; 95% CI: 0.96, 11.29); among multiparous women (n=1,400), bb genotype was associated with decreased risk of hip fracture (OR bb vs. BB: 0.59; 95% CI: 0.42, 0.84). CONCLUSION: VDR Bsm I genotype was associated with risk of hip fracture in Utah women, and this effect was modified by parity status. Hormonal or lifestyle factors related to parity may underlie this interaction.

Aged↗
PubMed2003

Biomass allocation, growth, and photosynthesis of genotypes from native and introduced ranges of the tropical shrub Clidemia hirta.

We tested the hypothesis that the tropical shrub Clidemia hirta appears more shade tolerant and is more abundant in its introduced than native range because of genetic differences in resource acquisition, allocation, and phenotypic plasticity between native and introduced genotypes. We examined growth, biomass allocation, and photosynthetic parameters of C. hirta grown in a greenhouse from seed collected from four populations in part of its native range (Costa Rica) and four populations in part of its introduced range (Hawaiian Islands). Six-month-old seedlings were placed in high (10.3-13.9 mol m(-2) day(-1)) or low (1.4-4.5 mol m(-2) day(-1)) light treatments and grown for an additional 6 months. Our study provided little evidence that Hawaiian genotypes of C. hirta differed genetically from Costa Rican genotypes in ways that would contribute to differences in habitat distribution or abundance. Some of the genetic differences that were apparent, such as greater allocation to stems and leaf area relative to whole plant biomass in Costa Rican genotypes and greater allocation to roots in Hawaiian genotypes, were contrary to predictions that genotypes from the introduced range would allocate more biomass to growth and less to storage than those from the native range. Hawaiian and Costa Rican genotypes displayed no significant differences in relative growth rates, maximal photosynthetic rates, or specific leaf areas in either light treatment. In the high light environment, however, Hawaiian genotypes allocated more biomass to reproductive parts than Costa Rican genotypes. Phenotypic plasticity for only 1 of 12 morphological and photosynthetic variables was greater for Hawaiian than Costa Rican genotypes. We conclude that genetic shifts in resource use, resource allocation, or plasticity do not contribute to differences in habitat distribution and abundance between the native and introduced ranges of C. hirta.

Biomass↗
PubMed2005

Molecular epidemiology of hepatitis C among drug users in Flanders, Belgium: association of genotype with clinical parameters and with sex- and drug-related risk behaviours.

The aim of this study was to determine the genotypic variation of hepatitis C among drug users in Flanders and to relate the distribution of genotypes to the characteristics of the population. Hepatitis C virus RNA (HCV-RNA) quantification and genotyping was performed on stored samples from 161 anti-HCV-positive injecting and non-injecting drug users. Information on sociodemographic status, drug-related risk behaviour and sexual risk behaviour was available for each drug user. HCV-RNA was present in 152 of 161 samples (94.4%). Genotype 1 was predominant (48.7%), followed by genotype 3 (41.2%), genotype 4 (8.8%) and genotype 2 (1.4%). In the multivariate analysis, lack of a history of injecting drug use was confirmed as a statistically significant predictor for infection with genotype 1. Predictors for infection with genotype 3 were the presence of anti-HBc antibodies and a history of injecting drug use. Being tattooed emerged as a statistically significant predictor for infection with genotype 4. The 94.4% prevalence of HCV-RNA among anti-HCV-positive drug users was considerably higher than the 54-86% chronicity rate found globally among HCV-infected patients. The results of this study suggest the existence of separate transmission networks for injecting drug users and non-injecting drug users. Finally, the results suggest that tattooing practices play a role in the spread of HCV among drug users.

Adult↗
PubMed2005

Parallel genotypic adaptation: when evolution repeats itself.

Until recently, parallel genotypic adaptation was considered unlikely because phenotypic differences were thought to be controlled by many genes. There is increasing evidence, however, that phenotypic variation sometimes has a simple genetic basis and that parallel adaptation at the genotypic level may be more frequent than previously believed. Here, we review evidence for parallel genotypic adaptation derived from a survey of the experimental evolution, phylogenetic, and quantitative genetic literature. The most convincing evidence of parallel genotypic adaptation comes from artificial selection experiments involving microbial populations. In some experiments, up to half of the nucleotide substitutions found in independent lineages under uniform selection are the same. Phylogenetic studies provide a means for studying parallel genotypic adaptation in non-experimental systems, but conclusive evidence may be difficult to obtain because homoplasy can arise for other reasons. Nonetheless, phylogenetic approaches have provided evidence of parallel genotypic adaptation across all taxonomic levels, not just microbes. Quantitative genetic approaches also suggest parallel genotypic evolution across both closely and distantly related taxa, but it is important to note that this approach cannot distinguish between parallel changes at homologous loci versus convergent changes at closely linked non-homologous loci. The finding that parallel genotypic adaptation appears to be frequent and occurs at all taxonomic levels has important implications for phylogenetic and evolutionary studies. With respect to phylogenetic analyses, parallel genotypic changes, if common, may result in faulty estimates of phylogenetic relationships. From an evolutionary perspective, the occurrence of parallel genotypic adaptation provides increasing support for determinism in evolution and may provide a partial explanation for how species with low levels of gene flow are held together.

Adaptation, Biological↗
PubMed2004

Hepatitis B virus genotype D prevails in patients with persistently elevated or normal ALT levels in Turkey.

BACKGROUND: The clinical relevance of hepatitis B virus (HBV) genotypes are poorly understood and it is unclear if the prevalence of HBV genotypes differs with the various clinical features of HBV carriers. The aim of our study was to examine the prevalence of the HBV genotype in a group of patients with chronic hepatitis B, compared to a group with chronic inactive hepatitos B surface antigen (HbsAg) carriers. PATIENTS AND METHODS: HBV genotypes were determined in 32 patients with chronic hepatitis B and in 12 chronic inactive HBsAg carriers. 35 males and nine females with a mean age of 33.95 +/- 13.04 were studied. Serum samples were examined for the presence of HBV DNA by polymerase chain reaction (PCR). Samples negative in first round PCR were further amplified with nested PCR. The PCR product was sequenced with the Cy5/5.5 dye primer kit on a Long Read Tower automated DNA sequencer. RESULTS: HBV DNA was detectable in 29 (66%) and 44 (100%) patients by the PCR with universal primers and nested-PCR, respectively. All patients were found to be infected with HBV genotype D. Genotype D was the only detected type found in different clinical forms of chronic HBV infection, in all hepatitis B e antigen (HbeAg)-positive and negative patients, in all patients who had elevated or normal alanine transaminase (ALT) levels and in all ages. CONCLUSION: In the present study we could not find any association between genotype D and distinct clinical phenotypes. Genotype D is the predominant type among hepatitis B carriers residing in our region and is not associated with more severe liver diseases. This genotype did not influence clinical manifestations in carriers with chronic hepatitis B virus infection. However, additional large-scale longitudinal studies are needed to find the relationship of HBV genotypes to liver disease severity and clinical outcomes.

Adult↗
PubMed2006

Difference of HBV genotype distribution between acute hepatitis and chronic hepatitis in Japan.

BACKGROUND: Recently genotype A which is rare in the patients in chronic hepatitis B (CHB) was frequently noted in patients with acute hepatitis B (AHB). To investigate their clinical and virological features, we studied the AHB patients in the past 5 years. PATIENTS AND METHODS: 98 patients with AHB and 80 patients with CHB admitted to our hospital between 1998 and 2003 were studied. RESULTS: Genotype A was not found in CHB but was frequently noted in AHB (p < 0.001). Comparison of the clinical features of acute hepatitis between the two major genotypes, A and C, homosexual and heterosexual with multiple partners were frequently seen among genotype A patients (p < 0.001). On the other hand, infection from steady partner showed a tendency to be more frequent in genotype C (p = 0.065). In genotype A, the levels of HBVDNA on admission was higher (p = 0.007) and AHB has significantly more frequently progress to chronic infection than in genotype C (p = 0.028). Phylogenetic analysis of genotype A revealed that almost all strains from homosexual men belonged not to the African type A1 but to the Western type A2. CONCLUSION: Genotype A has increased recently among AHB in Japan. This fact may correlate to promiscuous intercourse in high risk group. Prophylactic efforts should be considered to prevent the prevailing of genotype A.

Acute Disease↗
PubMed1993

Independent introduction of two major HIV-1 genotypes into distinct high-risk populations in Thailand.

To investigate the genetic heterogeneity and epidemiological distribution of human immunodeficiency virus type 1 (HIV-1) in Thailand, we determined proviral sequences for 63 HIV-1-infected patients in various risk groups from all over the country between April and July, 1991. Two distinct genotypes of HIV-1, A and B, were found to segregate by mode of transmission. Of 29 sexually infected patients, 25 (86%) had HIV-1 of genotype A and 4 (14%) had genotype B. Among 29 injecting drug users, probably parenterally infected, only 7 (24%) had genotype A and 22 (76%) had genotype B. This segregation is unlikely to have arisen by chance (p < 0.001). No patient was found to have dual infection. Nucleotide divergence averaged 3.4% among genotype-A-infected patients and 3.5% among genotype-B-infected patients, but 22.0% between the genotypes. 37 of 40 isolates (both genotypes) had the GPGQ tetrapeptide at the tip of the V3 loop, which is common in African HIV-1 strains but rare in North American and European strains, where the GPGR motif predominates. These findings suggest that the waves of HIV-1 infection in injecting drug users and in sexually infected patients in Thailand may not be epidemiologically linked. The nucleotide divergence data point to the separate introductions of the two genotypes in Thailand. Further studies in Thailand and neighbouring countries will be useful in the design and selection of candidate HIV vaccines.

Amino Acid Sequence↗
PubMed2006

N-Acetyltransferase-1 gene polymorphisms and correlation between genotype and its activity in a central Chinese Han population.

BACKGROUND: We investigated the arylamine N-acetyltransferase-1 (NAT1) gene polymorphisms and the correlation between genotype and phenotype in a Chinese Han population. METHODS: Peripheral blood from 140Han people were collected and analyzed for NAT1 genotypes by allele-specific PCR combining with PCR-based restriction fragment length polymorphism-based procedure. The NAT1 phenotype were determined according to the NAT1 enzyme kinetics in leukocytes by HPLC method and the values of intrinsic clearance (Cl(int)) and V(max) and Michaelis constant (K(m)) of NAT1 were calculated. RESULTS: The NAT1 genotype of Chinese Han populations was distinguished accurately and the NAT1 activity were detected in 32 objects with different genotypes. The allelic frequencies of NAT1*3, NAT1*4, NAT1*10 and NAT1*11 from 140 Han people, were 0.082, 0.496, 0.40 and 0.022, respectively. Compared with the activity of wild genotype NAT1 *4/*4, the activity of the homozygote or heterozygote NAT1*10 genotype which includes the NAT1 *4/*10, the NAT1 *10/*10 and the NAT1 *3/*10 was significantly high (p<0.05). The activity of the NAT1 *11/*11 and NAT1 *4/*11 was lower than that of the homozygote or heterozygote NAT1*10 genotype (p<0.05), but no difference with the activity of wild genotype and the NAT1 *4/*3 and NAT1 *3/*3. CONCLUSION: The distribution of the NAT1 genotype in a Chinese Han population was different from that in other countries. The activity of NAT1 showed significant variance from leukocytes with different genotypes.

Arylamine N-Acetyltransferase↗
PubMed2004

Contribution of age, body size, and CYP2C9 genotype to anticoagulant response to warfarin.

OBJECTIVE: Our objective was to assess the contribution of CYP2C9 genotype, age, body size, and vitamin K and lipid status to warfarin dose requirements. METHODS: Patients with stable warfarin dose requirements and an international normalized ratio (INR) of the prothrombin time within the target range of 2.0 to 3.0 were recruited to the study. On arrival at the clinic in the morning, after an overnight fast, a blood sample was taken from each patient for CYP2C9 genotyping and for determination of venous INR and plasma vitamin K, R- and S-warfarin, and triglyceride concentrations. RESULTS: A total of 121 patients were recruited to the study. CYP2C9 genotyping showed that 74 patients were homozygous wild-type (*1/*1), 30 were heterozygous *1/*2, and 15 were heterozygous *1/*3 genotype. One patient was found to have the genotype *2/*3, and another was found to have the genotype *3/*3. The mean warfarin daily dose requirement in milligrams fell from 4.06 +/- 1.72 mg in homozygous wild-type patients to 3.63 +/- 1.78 mg for *1/*2-positive patients and 2.70 +/- 1.36 mg for *1/*3-positive patients. The multiple linear regression model for warfarin dose indicated significant contributions from age (r = 0.41, P <.001), genotype (r = 0.24, P <.005), and age and genotype together (r = 0.45, P <.005). Although there were significant linear correlations between warfarin dose and body surface area (r = 0.21, P =.02), body weight (r = 0.25, P =.005), and plasma vitamin K concentration (r = 0.18, P <.05), none of these variables made a significant contribution to the regression model for warfarin dose. CYP2C9 genotype had a significant effect on S-warfarin clearance (r = 0.34, P <.0001) but none on R-warfarin clearance. CONCLUSION: This study showed that age and CYP2C9 polymorphism affect warfarin dose requirements in patients receiving long-term therapy and having stable control of anticoagulation. It is anticipated that using dosing regimens modified to take into account the contribution of age and CYP2C9 genotype has the potential to improve the safety of warfarin therapy.

Adult↗
PubMed2004

Association between TNF-alpha and TGF-beta genotypes in infants and parental history of allergic rhinitis and asthma.

The development and expression of allergic rhinitis and asthma may be influenced by the elaboration of specific cytokines. Cytokine genotypes moderate illness severity in a variety of inflammatory disorders. Cytokine genotyping was performed on 124 infants (85% white, 57% male) to determine whether specific cytokine genotypes are associated with a parental history of allergic rhinitis and/or asthma. DNA was extracted from buccal brushings and assayed for tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-beta1 genotypes using polymerase chain reaction-sequence specific primer technology. Outcomes consisted of parental history of allergy and asthma, and results were evaluated by logistic regression. TNF-alpha and TGF-beta genotypes were related to maternal and/or paternal history of allergic rhinitis and asthma, respectively. The frequencies of the genotype associated with high production of TNF-alpha were 41% versus 18% in infants with and without a parental history of allergic rhinitis, respectively (p < 0.01). The frequencies of the genotype associated with low production of TGF-beta1 were 14% versus 1% in infants with and without a parental history of asthma, respectively (p < 0.01). There were no associations between IFN-gamma, IL-6, and IL-10 genotypes and any of the outcome parameters. These results suggest a role for TNF-alpha and TGF-beta1 genotypes in the pathogenesis of allergic rhinitis and asthma, respectively. If confirmed by future studies, cytokine genotyping may be a useful tool for identifying at-risk infants who may benefit from the selective use of preventative and/or early intervention treatments for these disorders.

Asthma↗
PubMed2004

Genotypes associated with myocardial infarction risk are more common in African Americans than in European Americans.

OBJECTIVES: This study was designed to describe the frequencies of multiple myocardial infarction (MI) risk-associated genotypes among different racial groups. BACKGROUND: Racial disparities in the prevalence of cardiovascular disease (CVD) are well known. Recent large Japanese case-control studies identified connexin-37 (GJA-4), plasminogen activator inhibitor-1 (PAI-1), and stromelysin-1 (MMP-3) polymorphisms as risk factors for MI, but the prevalence of these genotypes among different racial groups in the U.S. needs to be determined. METHODS: Genomic deoxyribonucleic acid from 95 healthy African Americans (AA) and 95 healthy European Americans (EA) was used for genotyping. Deoxyribonucleic acid containing the region of interest was amplified using the polymerase chain reaction, followed by genotyping using pyrosequencing. RESULTS: All three MI-risk genotypes were observed in both populations and were in Hardy-Weinberg equilibrium. The frequencies of two of the three "risk-associated" genotypes were significantly higher in the AA population: GJA4 C1019T T/T: AA, 20%, EA, 7% (p = 0.053); MMP3 -1171delA A/A: AA, 78%, EA, 24% (p < 0.001); PAI-1 -668delG G/G: AA, 55%, EA, 16% (p < 0.001). The likelihood of two or more high-risk genotypes was 3.3% among EA subjects and 51% in the AA group (p < 0.001). We found that 9.1% of AA had all three high-risk genotypes, compared with 0% among the EA group (p = 0.0097). CONCLUSIONS: We found higher frequencies of disease-associated genotypes in AA than in EA. Our results also show that more AA than EA carry multiple risk-associated genotypes. Future studies need to assess whether such genetic profiles predict adverse outcomes in U.S. populations and contribute to racial disparities in CVD burden.

Black or African American↗
PubMed2000

Genotyping of alpha-antitrypsin in ten Croatian families.

OBJECTIVES: The aims of the study were to determine alpha-antitrypsin (AAT) genotype by a simple DNA-based method and to investigate the association of AAT genotype and serum AAT concentration in a group of ten families. METHODS AND RESULTS: AAT genotype was determined by PCR-RFLP and serum concentration by radial immunodiffusion in samples from each member of ten families (mother, father, and child/children). In the group of parents, five normal genotypes, Pi MM, with a normal serum AAT concentration, and fifteen Pi MZ genotypes, four of them with slightly decreased (43%-66% of the mean) AAT concentration were detected. In the group of children, particular genotypes followed the mode of inheritance. There were eight Pi MZ, three of them with slightly decreased (52%-60% of the mean) AAT concentration, and five Pi ZZ genotypes with considerably decreased (24%-45% of the mean) AAT concentration. CONCLUSIONS: PCR-RFLP is the method of choice for AAT genotyping. AAT concentration is not a reliable biochemical marker of AAT deficiency. Determination of AAT genotype in family studies allows the risk of deficient allele inheritance to be followed up and assessed. Early diagnosis of a deficient AAT genotype contributes to the success of currently widely available AAT replacement therapy.

Adolescent↗