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At least 145 records · Page 8Linked to original sources
PubMed2002

Coagulation factor XII activity, but not an associated common genetic polymorphism (46C/T),is linked to recurrent miscarriage.

OBJECTIVE: To investigate whether a factor XII genetic polymorphism is associated with first-trimester embryonal loss. DESIGN: Prospective case-control study. SETTING; Nagoya City University Hospital. PATIENT(S): Eighty-three patients with a history of two or more unexplained first-trimester recurrent miscarriages and 67 controls with no obstetric complications or history of miscarriage. MAIN OUTCOME MEASURE(S): Plasma factor XII activity, a genetic polymorphism (46 C-->T) of factor XII, lupus anticoagulant, and beta(2)glycoprotein I dependent anticardiolipin antibodies. RESULT(S): Ten of the 83 patients and 1 of the 67 controls had decreased factor XII activity; the difference in frequency was statistically significant. Wild-type (CC), heterozygote (CT), and homozygote (TT) allele patterns were observed in 8, 36, and 39 patients, respectively, compared with 11, 20, and 36 of the patients and controls, respectively. The mean (+/- SD) corresponding factor XII activity was 154.8 +/- 44.8%, 112.7 +/- 30.2%, and 66.2 +/- 29.2% in patients and 164.6 +/- 26.7%, 114.3 +/- 28.1%, and 70.4 +/- 18.1% in controls. The two groups did not differ in the frequency of the T allele or categories of factor XII activity. CONCLUSION(S): Factor XII activity overall, but not the 46C/T common genetic polymorphism, is associated with recurrent miscarriage.

Abortion, Habitual↗
PubMed2000

[Study on beta 2 adrenergic receptor genetic polymorphisms in asthmatics in the people of the Han nationality of northern China].

OBJECTIVE: To analyze the association between beta 2-AR genetic polymorphism and asthma in the people of the Han nationality of northern China. METHODS: Allele Specific-PCR techniques were used to determine 16, 27 and 164 locus alleles of beta 2-AR genetic polymorphisms in 58 unrelated patients with asthma and 89 healthy controls from the people of the Han nationality of northern China. RESULTS: (1) The distribution frequency of genotype beta 2-AR 16 loci: Arg/Arg genotype accounts for 13%, Arg/Gly 76% and Gly/Gly 11%. The beta 2-AR 27 loci: Gln/Gln genotype accounts for 36%, Gln/Glu 55% and Glu/Glu 9%. The beta 2-AR 164 loci: Thr/Thr genotype accounts for 30%, Thr/Ile 53% and Ile/Ile 17%. (2) The frequency of genotype beta 2-AR 16 loci in asthmatics: Arg/Arg genotype accounts for 24%, Arg/Gly 45% and Gly/Gly 31%. There was a significant increase in the frequency of Gly/Gly genotype in asthmatics compared with healthy group(OR = 4.0, 95% CI 1.7-9.7), but there was no significant difference in the allele frequency of asthmatics compared with healthy group. The frequency of genotype beta 2-AR 27 loci in asthmatics: Gln/Gln genotype accounts for 34%, Gln/Glu 56% and Glu/Glu 10%. There was no significant difference in the allele frequency of asthmatics compared with healthy group. The frequency of genotype beta 2-AR 164 loci in asthmatics: Thr/Thr genotype accounts for 10%, Thr/Ile 83% and Ile/Ile 7%. There was no significant difference in the frequency of Ile/Ile genotype in asthmatics compared with healthy group, and in the allele frequency of asthmatics compared with healthy group. In addition, our study reveals that beta 2-AR 16 locus genetic polymorphism is in association with asthmatic severity. CONCLUSIONS: These results suggest that beta 2-AR 16 locus genetic polymorphism is correlated with asthma severity in the people of the Han nationality of northern China.

Adolescent↗
PubMed2001

[Progress in researches on the relationship between genetic polymorphisms of alcohol-metabolizing enzymes and cancers].

Genetic polymorphism of carcinogen-metabolizing enzymes is one of the important aspects of the genetic susceptibility to cancer. The enzymes involved in alcohol metabolism include mainly alcohol dehydrogenase(ADH), aldehyde dehydrogenase(ALDH) and cytochrome P450 2E1(CYP2E1), which all appear to be polymorphic. Several recent studies show that the genetic polymorphisms of alcohol-metabolizing enzymes are associated with some cancers such as liver cancer, stomach cancer and esophageal cancer. But there are also the inconsistent results.

Alcohol Dehydrogenase↗
PubMed2003

Analysis of genetic polymorphisms of steroid 5alpha-reductase type 1 and 2 genes in Korean men with androgenetic alopecia.

BACKGROUND: Genetic polymorphisms of steroid 5alpha-reductase have been studied in androgenetic alopecia in Caucasians, but the genes encoding the two isoenzymes were not associated with male pattern baldness. Genetic polymorphisms and ethnic variations have not been studied for Asians, although it is suggested that racial difference could exist and influence clinical phenotypes. OBJECTIVE: The purpose of our study is to investigate the genetic polymorphisms of steroid 5alpha-reductase type 1 and 2 (SRD5A1 and SRD5A2) genes in Korean population, and to study the association of these polymorphisms with the development, clinical types (female or male pattern) and therapeutic response of androgenetic alopecia. METHODS: Sixty-six patients with androgenetic alopecia and controls consisted of 92 healthy men were included. Twenty-four patients were treated with finasteride for at least 6 months, and clinical responses were assessed by a simple classification. For type 1 isoenzyme, HinfI and NspI restriction fragment length polymorphisms (RFLPs) were detected using polymerase chain reaction method. For type 2 isoenzyme, RsaI RFLPs detected valine/leucine polymorphisms at codon 89, and MowI RFLPs detected alanine/threonine polymorphisms at codon 49. RESULTS: We could not find any significant associations of the genetic polymorphisms of these two isoenzyme genes with androgenetic alopecia in Koreans (P>0.05). These polymorphisms were not associated with the clinical types of baldness or the response to finasteride (P>0.05). CONCLUSION: These results suggest that polymorphisms of SRD5A1 and SRD5A2 genes may not be directly associated with the development of baldness or generation of different clinical phenotypes.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2003

Interleukin-1beta genetic polymorphism influences the effect of cytochrome P 2C19 genotype on the cure rate of 1-week triple therapy for Helicobacter pylori infection.

OBJECTIVES: Genetic polymorphism of interleukin (IL)-1beta is associated with differences in gastric acid suppression in response to Helicobacter pylori (H. pylori) infection. Thus, the polymorphism might affect H. pylori eradication therapy, as antibiotics used in treatment regimens may be acid sensitive. In this study, we examined the impact of IL-1beta genetic polymorphism on the cure rate of triple therapy for H. pylori in relation to cytochrome P (CYP) 2C19 genotype and antibiotic resistance. METHODS: A total 249 patients with peptic ulcer disease were randomized to receive one of the following regimens: amoxicillin and clarithromycin together with omeprazole, lansoprazole, or rabeprazole. CYP2C19 and IL-1beta-511 genetic polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The intention-to-treat-based overall cure rate was 74.3% (95% CI=68-79%). In the normal acid secretion IL-1beta genotype group, the cure rate among CYP2C19 poor metabolizers (93.3%, 95% CI=56-99%) was significantly higher than among subjects in the CYP2C19 homozygous (60.0%, 95% CI=38-78%) and heterozygous (63.6%, 95% CI=46-78%), i.e., extensive metabolizer, groups (p<0.05). In the low acid secretion IL-1beta genotype group, there was no difference in the cure rate among the CYP2C19 genotype groups. Multiple logistic regression analysis identified susceptibility to clarithromycin (p<0.0001) and CYP2C19 genotype status (p=0.03) as significant independent factors for treatment failure. CONCLUSION: IL-1beta genetic polymorphism, although not an independent factor in treatment outcome, influences the impact of the CYP2C19 genotype on the cure rate of 1-wk triple therapy for H. pylori infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Aromatic DNA adducts in coke-oven workers, in relation to exposure, lifestyle and genetic polymorphism of metabolic enzymes.

OBJECTIVE: This study investigates the effect of multiple factors, including exposure to polycyclic aromatic hydrocarbons (PAHs), lifestyle, genetic polymorphism of cytochrome P450 (CYP)1A1, glutathione transferase (GST)M1, GSTP1, N-acetyltransferase (NAT)2 and gene p53, as well as any family history of cancer, on DNA adduct levels in coke-oven workers. METHODS: Sixty-five coke-oven workers employed at the largest iron-steel factory in China were recruited for the study. Personal data were collected at the interview. DNA adduct levels in total white blood cells (WBCs) were detected using 32P-postlabeling techniques. Genetic polymorphisms were analyzed by polymerase chain reaction (PCR) methods. RESULTS: The subjects were divided into low and high exposure groups, according to personal exposure to PAHs. The mean adduct value was 1.57 (range 0.54 to 4.35) per 10(8) nucleotides. A tendency for increased levels of DNA adducts in the high exposure group was observed, compared with the low exposure group (P = 0.07). In the low exposure group, DNA adducts were found to be positively associated with urinary cotinine (r = 0.44, P = 0.01). The rare allele homozygotes of CYP1A1 showed significantly higher DNA adduct levels than those of other CYP1A1 genotypes. Individuals with the NAT2 wild type had significantly increased DNA adduct levels than those with other NAT2 genotypes in the high exposure group. The p53 genetic polymorphism revealed a significantly positive effect on DNA adducts formation. There was a significantly higher adduct level in the subjects with a family history of cancer than those without, in the high exposure category. CONCLUSIONS: Effects of several variables, such as smoking, genetic polymorphism of 2 CYP1A1, NAT2, and gene p53, and a family history of cancer on DNA adduct levels were found, suggesting that these variables should be considered when evaluating the genotoxic effect of occupational exposure to PAHs using WBCs DNA adducts.

Arylamine N-Acetyltransferase↗
PubMed2006

Susceptibility to pre-eclampsia is associated with multiple genetic polymorphisms in maternal biotransformation enzymes.

BACKGROUND/AIMS: Probably no single gene is responsible for pre-eclampsia, but the disease merely is the result of polymorphisms in several genes in association with environmental factors. We therefore studied the simultaneous occurrence of several genetic polymorphisms in biotransformation enzymes in women who had developed pre- eclampsia, either with or without the HELLP syndrome, in comparison with healthy controls. METHODS: The results of two previous studies on genetic polymorphisms in glutathione S-transferases P1, M1 and T1, epoxide hydrolase (EPHX) and cytochrome P4501A1 (CYP1A1) in 167 women with a history of pre-eclampsia and in 110 controls were combined. chi(2) analyses were used for statistical evaluation of the number of polymorphisms between cases and controls. RESULTS: There was a significant association with the number of genetic polymorphisms in biotransformation enzymes, pointing at an increased toxification or decreased detoxification, in women with a history of pre-eclampsia, as compared to healthy controls (p < 0.001). CONCLUSION: Women withthe simultaneous occurrence of two or more genetic polymorphisms in the above-mentioned biotransformation enzymes, most probably resulting in a disturbed detoxification capacity, may be at increased risk for pre-eclampsia.

Adult↗
PubMed2003

Influence of genetic polymorphisms of CYP1A1 and GSTM1 on the urinary levels of 1-hydroxypyrene.

The aim of the present study is to evaluate the influence of the genetic polymorphism of two enzymes involved in the biotransformation of xenobiotics, cytochrome P450 1A1 (CYP1A1) and glutathione-S-transferase M1 (GSTM1), on the urinary levels of 1-hydroxypyrene (1-OH-P) in workers exposed to polycyclic aromatic hydrocarbons (PAHs) and in unexposed workers (controls). The study group consisted of 30 controls recruited among employees of a service company and 171 PAHs-exposed workers from two electric steel plants and an iron foundry (all males, ranging between 18 and 60 years of age). Determination of airborne PAHs and urinary 1-OH-P was performed by high-performance liquid chromatography (HPLC) with fluorimetric detection. Polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) was used to determine the genetic polymorphisms of CYP1A1 (CYP1A1*2A and CYP1A1*2B) and GSTM1. No influence of the genetic polymorphism of CYP1A1 and GSTM1 on the urinary levels of 1-OH-P was observed in this study.

Adolescent↗
PubMed2005

[Genetic polymorphism and drug interactions: their importance in the treatment of pain].

OBJECTIVES: To evaluate the impact of certain genetic polymorphisms on variable responses to analgesics SOURCES: Systematic review, by means of a structured computerized search in the Medline database (1966-2004). Articles in English and French were selected. References in relevant articles were also retrieved. MAIN FINDINGS: Most analgesics are metabolized by CYP isoenzymes subject to genetic polymorphism. NSAIDs are metabolized by CYP2C9; opioids described as "weak" (codeine, tramadol), anti-depressants and dextromethorphan are metabolized by CYP2D6 and some "potent" opioids (buprenorphine, methadone or fentanyl) by CYP3A4/5. After the usual doses have been administered, drug toxicity or, on the contrary, therapeutic ineffectiveness may occur, depending on polymorphism and the substance. Drug interactions mimicking genetic defects because of the existence of CYP inhibitors and inducers, also contribute to the variable response to analgesics. Some opioids are substrates of P-gp, a transmembrane transporter also subject to genetic polymorphism. However, P-gp could only play a minor modulating role in man on the central effects of morphine, methadone and fentanyl. CONCLUSION: In the near future, pharmacogenetics should enable us to optimize therapeutics by individualizing our approach to analgesic drugs and making numerous analgesics safer and more effective. The clinical usefulness of these individualized approaches will have to be demonstrated by appropriate pharmacoeconomic studies and analyses.

Analgesics↗
PubMed2005

Genetic polymorphisms of selected DNA repair genes, estrogen and progesterone receptor status, and breast cancer risk.

PURPOSE: Genetic polymorphisms of DNA repair genes seem to determine the DNA repair capacity, which in turn may affect the risk of breast cancer. To evaluate the role of genetic polymorphisms of DNA repair genes in breast cancer, we conducted a hospital-based case-control study of Korean women. EXPERIMENTAL DESIGN: We included 872 incident breast cancer cases and 671 controls recruited from several teaching hospitals in Seoul from 1995 to 2002. Twelve loci of selected DNA repair genes were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (XRCC2 Arg188His, XRCC4 921G > T, XRCC6 1796G > T, LIG4 1977T/C, RAD51 135G > C, 172G > T, RAD52 2259C > T, LIG1 551A > C, ERCC1 8092A > C, 354C > T, hMLH1 -93G > A, and Ile219Val). RESULTS: We found that the RAD52 2259 CT or TT, hMLH1 -93 GG, and ERCC1 8092 AA genotypes were associated with breast cancer risk after adjustment for known risk factors [odds ratio (OR), 1.33; 95% confidence interval (95% CI), 1.02-1.75; OR, 1.31; 95% CI, 0.99-1.74; and OR, 0.58; 95% CI, 0.38-0.89, respectively]. When Bonferroni's method was used to correct for multiple comparisons for nine polymorphisms with P = 0.005, all of these associations were not significant. However, the effects of RAD52 2259 CT or TT and ERCC1 354 CT or TT genotypes were more evident for the estrogen/progesterone receptor-negative cases (OR, 2.03; 95% CI, 1.24-3.34 and OR, 1.99; 95% CI, 1.35-2.94, respectively). CONCLUSION: Our findings suggest that genetic polymorphisms of RAD52, ERCC1, and hMLH1 may be associated with breast cancer risk in Korean women.

Adaptor Proteins, Signal Transducing↗
PubMed1993

Genetic polymorphism of cytochrome P4502E1 in a Swedish population. Relationship to incidence of lung cancer.

Genetic polymorphism of CYP2E1 was investigated among 195 Swedish patients with lung cancer and 206 controls. Three different polymorphic sites were found, all in introns, using RFLP and the restriction enzymes DraI, RsaI and TaqI. The frequencies of the rare alleles were 0.08-0.18 and much lower than previously described among Japanese. No significant difference in distribution of the polymorphic alleles between controls and lung cancer patients was evident, in contrast to results of a previous Japanese study. However, examination of a polymorphic site in the 5'-flanking region, within a putative binding motif for the hepatic transcription factor HNF-1, revealed a significantly less frequent distribution of the mutated allele (c2) among the lung cancer patients as compared to controls. It is concluded that major interethnic differences exist in the genetic polymorphism of CYP2E1 and that people carrying the c2 allele might be at lower risk for developing lung cancer.

Base Sequence↗
PubMed2006

Genetic polymorphisms, hormone levels, and hot flashes in midlife women.

OBJECTIVE: Hot flashes disrupt the lives of millions of women each year. Although hot flashes are a public health concern, little is known about risk factors that predispose women to hot flashes. Thus, the objective of this study was to examine whether sex steroid hormone levels and genetic polymorphisms in hormone biosynthesis and degradation enzymes are associated with the risk of hot flashes. METHODS: In a cross-sectional study design, midlife women aged 45-54 years (n=639) were recruited from Baltimore and its surrounding counties. Participants completed a questionnaire and donated a blood sample for steroid hormone analysis and genotyping. The associations between genetic polymorphisms and hormone levels, as well as the associations between genetic polymorphisms, hormone levels, and hot flashes were examined using statistical models. RESULTS: A polymorphism in CYP1B1 was associated with lower dehydroepiandrosterone-sulfate (DHEA-S) and progesterone levels, while a polymorphism in CYP19 (aromatase) was associated with higher testosterone and DHEA-S levels. Lower progesterone and sex hormone binding globulin levels, lower free estradiol index, and a higher ratio of total androgens to total estrogens were associated with the experiencing of hot flashes. A polymorphism in CYP1B1 and a polymorphism in 3betaHSD were both associated with hot flashes. CONCLUSION: Some genetic polymorphisms may be associated with altered levels of hormones in midlife women. Further, selected genetic polymorphisms and altered hormone levels may be associated with the risk of hot flashes in midlife women.

Aryl Hydrocarbon Hydroxylases↗
PubMed1982

Genetic polymorphism of coagulation factor XIIIB subunit in Japanese.

Genetic polymorphism of coagulation factor XIIIB subunit in Japanese has been described, using a thin-layer agarose gel isoelectric focusing followed by immunofixation. Phenotypes of factor XIIIB subunit were essentially classified into three common patterns A, B and AB. It is estimated that the phenotypes are determined by two codominant alleles. A new rare variant B' has been detected in Japanese. Gene frequencies calculated from 304 individuals showed FXIII-BA = 0.735, FXIII-BB = 0.252 and FXIII-BB' = 0.013, respectively. The distribution of phenotypes fitted the Hardy-Weinberg equilibrium.

Child↗
PubMed1993

Genetic polymorphisms of salivary proteins in the rat.

Two genetic polymorphisms of salivary proteins were found by polyacrylamide gel electrophoresis among inbred strains of rats. Both proteins (RSP-1 and RSP-2) were inherited as a single autosomal trait. The loci were designated as Rsp-1 (rat salivary protein-1) and Rsp-2. Rsp-1 had two codominant alleles (Rsp-1a, Rsp-1b), and Rsp-2 had two alleles (Rsp-2a, and Rsp-2b); Rsp-2a was dominant over Rsp-2b. The Rsp-1 locus is not linked with the linkage groups (LGs) I, II, IV, V and the LGs containing Acp-2 and Pg-1. The Rsp-2 is not linked with the LGs I, II, V, X and the LGs containing Amy-1, Es-6 and Pg-1.

Alleles↗
PubMed2006

CYP2C19 genetic polymorphism in Thai, Burmese and Karen populations.

The genetic polymorphism of CYP2C19 was examined in three Southeast Asian populations. This study was conducted in 774 Thais, 127 Burmeses and 131 Karens. Genomic DNA was extracted from leucocytes and analyzed by the PCR-RFLP technique. Genotype analysis revealed that the allele frequencies of CYP2C19*1, CYP2C19*2 and CYP2C19*3 in the Thais were 0.68, 0.29 and 0.03, respectively, and those of the Burmese population were 0.66, 0.30 and 0.04, respectively. For Karens, the minority ethnic in Mynmar, the allele frequencies of CYP2C19*1, CYP2C19*2 and CYP2C19*3 were 0.71, 0.28 and 0.01, respectively. The prevalence of PM estimated from genotype data among these three ethnic populations were 9.2%, 11.0%, and 8.4%, respectively. The PM phenotype and the frequencies of CYP2C19 defective alleles, particularly CYP2C19*3 among these three Southeast Asian ethnics appeared to be lower than other Asian populations. Lower prevalence of CYP2C19 PM suggests that these ethnics may have different capacity to metabolize drugs that are substrates of CYP2C19. Certain drug dosage regiments should be considered differently for Asian populations.

Adult↗
PubMed1980

Human neutral alpha-glucosidase C: genetic polymorphism including a "null" allele.

We describe a genetic polymorphism of human neutral alpha-glucosidase C, detected in lymphoid cells by a combination of starch gel electrophoresis and isoelectric focusing. The seven phenotypes observed appear to result from the expression of four different alleles. The distribution of the observed phenotypes fits the expected distribution predicted from calculated gene frequencies in Hardy-Weinberg equilibrium. Family studies are consistent with autosomal inheritance of the gene. The product of one of the alleles is unusual in that it is "silent," with an estimated gene frequency of .174 in an outbred white population. Approximately one-third of the population is heterozygous "null." Homozygosity for the allele has not been associated with any obvious disease state. This is the third example of a "null" allele which has a substantial gene frequency in an outbred population but does not appear to result in disease in the homozygous state.

Alleles↗
PubMed1997

[Genetic polymorphism in three indigenous ethnic populations of Dagestan].

Genetic, demographic, and biochemical studies of three isolated ethnic populations of Dagestan were performed. Two populations lived in their historical (highland and lowland) habitats, and one population migrated from highlands to lowlands, i.e., changed its environment. A substantial genetic differentiation with respect to eight biochemical systems and marital structure was found. Altitudinal variation was revealed in allelic frequencies of group-specific component (GC) and haptoglobin (HP). The frequency of allele GC * 1 decreased and that of allele HP * 1 increased as the altitude increased in the studied localities. The studied populations differed with respect to the average heterozygosity levels per locus. Both absolute heterozygosity levels and the pattern of interpopulation differences estimated for all of the eight biochemical markers considerably differed from those estimated for all markers except for GC and HP. These data indicate that the latter two biochemical systems are important for adaptation of the studied Dagestan populations. In surviving migrants from highlands to lowlands, the levels of inbreeding and genetic polymorphism were intermediate between these values for highlanders and native lowlanders. Earlier, the 30% selective mortality was revealed in migrants from highlands to lowlands during the first years of adaptation to new conditions. Those individuals who died had a higher inbreeding level, homozygosity, and physiological sensitivity. In this study, only surviving migrants were examined. Therefore, it may be suggested that the inadaptive (dying) part of migrants also differed from the adaptive (surviving) part in the higher HP * 1 and GC * 2 allelic frequencies.

Alleles↗
PubMed2002

Genetic polymorphisms of UDP-glucuronosyltransferases and their functional significance.

UDP-Glucuronosyltransferase (UGT), the microsomal enzyme responsible for glucuronidation reactions, exists as a superfamily of enzymes. Genetic polymorphism has been described for 6 of the 16 functional human UGT genes characterised to date, namely UGT 1A1, 1A6, 1A7, 2B4, 2B7 and 2B15. Since glucuronidation is an essential pathway for the elimination of a myriad of xenobiotics and endogenous compounds, genetic polymorphism of UGT is potentially of toxicological and physiological importance. However, functional significance has only been convincingly demonstrated for genetic polymorphism of UGT1A1. Apart from impaired bilirubin glucuronidation, the mutations responsible for Gilbert syndrome also affect the elimination of a limited number of xenobiotics. It has been proposed on the basis of altered catalytic activity of mutants of UGT 1A6, 1A7 and 2B15 that genetic polymorphism of these forms may be of toxicological significance, but this is yet to be proven.

Animals↗