Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genetic polymorphism”

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 793 records · Page 44Linked to original sources
PubMed2000

[Lung cancer risk and genetic polymorphism at the glutathione S-transferase P1 locus in male Japanese].

The glutathione S-transferases (GSTs) are widely expressed in mammalian tissues and involved in Phase II detoxification reactions. The GSTs form a supergene family consisting of four distinct families, named alpha (GSTA), mu (GSTM) theta (GSTT) and pi (GSTP). Several of the GST genes are polymorphic in humans and are currently being investigated as possible cancer-risk modifiers. Among the GST genes, we examined GSTP1 polymorphism in exon 5 among male lung cancer patients (n = 86, male Japanese) and male healthy controls (n = 80, male Japanese) by restriction fragment length polymorphism-polymerase chain reaction method. The cancer patients showed frequency of the GSTP1 mutated genotype (individuals having at least one mutant allele, 29.1%) very similar to that of the control subjects (28.8%). After adjusting for smoking status, no association was found between the GSTP1 mutated genotype and lung cancer risk (odds ratio: 0.95; 95% confidence interval: 0.48-1.90). When study subjects were divided into two subgroups based on smoking status, the GSTP1 mutated genotype was not associated with an increased risk of lung cancer among smokers and non-smokers. These results suggest that GSTP1 polymorphism in exon 5 alone may not increase the risk of lung cancer in male Japanese.

Adult↗
PubMedDate not supplied

[Genetic polymorphism in glutathione S-transferase M1 and T1 in children with bronchial asthma].

Asthmatic (n = 100) and health (n = 104) children were compared for rates of homozygous deletions of the glutathione S-transferase class mu and theta genes (null genotypes, GSTM1"-" and GSTT1"-", respectively). The frequency of GSTM1"-" and GSTT1"-" genotypes in patients with bronchial asthma (BA) (52 [symbol: see text] 26%) were increased compared to healthy children (42 and 11%) (odds ratio (OR) for GSTM1"-" = 1.48; CI: 0.82-2.67; p = 0.16; OR for GSTT1"-" = 2.69; CI: 1.2-6.11; p = 0.0079). OR for GSTM1"-" and GSTT1"-"-combination was 5,12; CI: 0.55-119.5; p = 0.107. We conclude that null-genotypes are associated with susceptibility to BA in children. Passive smoking (PS) increased risk of BA for children with GSTM1"-" genotype, but not with GSTT1"-" genotype. The association of these genotypes was estimated with such clinical peculiarities of BA as polyvalent allergy, early development and heavy course. In the group of nonsmoking (NS) patients was found the statistically in significant association of individual null genotypes with any clinical peculiarities. Combination of null-genotypes in NS patients associated with early development of BA (OR = 6.5; CI: 0.78-64.95; p < 0.05), and combination of plus genotypes--with polyvalent allergy (OR = 7.35; CI: 1.07-63.44; p < 0.05). In the group of PS patients GSTM1"-" genotype was associated with early development of BA (OR = 9.0; CI: 1.02-203.3; p < 0.05) and GSTT1"-" genotype--with heavy course of disease (OR = 4.64; CI: 1.16-19.34; p < 0.05). Passive smoking was the risk factor for the unfavourable course of BA for the patients carrying GSTM1"-" genotype. Combination of plus genotypes protected PS patients from all unfavorable peculiarities of disease.

Adolescent↗
PubMed2001

[Genetic polymorphism of eight STR loci in the Han population in Henan province].

OBJECTIVE: To investigate the allele frequencies of eight short tandem repeats(STR) loci: TH01, FES, D19S400, D7S820, D16S539, D20S161, D3S1545 and D5S818 in Han population in Henan province. METHODS: DNA was extracted with phenol-chloroform from EDTA-blood samples of the unrelated individuals in Henan province and amplified with PCR technique. The PCR product was analyzed with the undenatured PAGE vertical electrophoresis and silver-stain. RESULTS: The authors got the frequencies of the eight loci. The heterozygosities of the eight loci are 0.66, 0.67, 0.80, 0.76, 0.79, 0.79, 0.78 and 0.78; the discrimination powers are 0.83, 0.83, 0.94, 0.91, 0.93, 0.93, 0.92 and 0.92. CONCLUSION: The heterozygosities of the eight loci are high and the frequencies are in good agreement with Hardy-Weinberg equilibrium, so the eight loci can be used in individual identification testing.

Alleles↗
PubMed2000

Genetic polymorphism of CYP2D6 in Karnataka and Andhra Pradesh population in India.

AIM: To study the prevalence of cytochrome P-450 2D6 (CYP2D6) polymorphism in Karnataka (KA) and Andhra Pradesh (AP) population. METHODS: Two hundred and eleven healthy human volunteers participated in the study (100 from KA and 111 from AP). At bed time, after voiding their bladder, the volunteers ingested 30 mg of dextromethorphan hydrobromide (DM). Urine samples were collected for 8 h. DM and its metabolite dextrorphan (DT) were estimated in the urine using HPLC. The metabolic ratio (DM/DT) was used for phenotyping. RESULTS: The prevalence of poor metabolisers (PM) in KA is 4% and AP is 1.8%. CONCLUSION: The frequency of PM phenotype in South Indian population is in between the Western and Oriental population.

Adolescent↗
PubMed2001

[Genetic polymorphism and variability of steroid hormone metabolism: connection with risk of developing breast neoplasms].

Endogenous estradiol is synthesized in the ovarian theca cells of premenopausal women or in the stromal adipose cells of the breast of postmenopausal women and in minor quantities in peripheral tissue. These cells, as well as breast cancer tissue, express all the necessary enzymes for this synthesis: CYP17, CYP11a, CYP19, hydroxysteroid hydrogenase, steroid sulphatase as well as enzymes further hydroxylating estradiol such as CYP1A1, CYP3A4, CYP1B1. Polymorphisms in these enzymes may have a possible role in the link between environmental estrogens and hormone-like substances and the interindividual risk of breast cancer.

Arylsulfatases↗
PubMed2001

Association of genetic polymorphisms in UGT1A1 with breast cancer and plasma hormone levels.

UDP-glucuronosyltransferases (UGTs) catalyze the detoxification and the elimination of a large number of endogenous and exogenous compounds in the liver and extrahepatic tissues. One of the UGT1A family members, UGT1A1, is involved in estradiol metabolism and, therefore, represents a candidate gene in breast carcinogenesis. A common insertion/deletion polymorphism in the TATA-box of the promoter region of UGT1A1 results in decreased initiation of transcription. In a previous study, we found a positive association between the UGT1A1 low-transcriptional alleles and premenopausal breast cancer risk in an African-American population. In the present study, we sought to determine whether the low-transcription UGT1A1 promoter allele, UGT1A1*28 [A(TA)(7)TAA], was associated with increased breast cancer risk among primarily Caucasian women in a nested case-control study within the Nurses' Health Study cohort. No significant association between the UGT1A1*28 [A(TA)(7)TAA] allele and breast cancer was observed. Compared with women homozygous for the UGT1A1*1 [A(TA)(6)TAA] allele, the relative risk was 0.80 (confidence interval, 0.49-1.29) for women homozygous for the UGT1A1*28 allele. The effect of the UGT1A1 genotype on plasma hormone levels in postmenopausal women not using hormone replacement was also evaluated, and overall, no significant differences in hormone levels by genotypes were observed. When restricted to women who had at least one UGT1A1*28 allele and a body mass index at blood draw of >27 kg/m(2), particularly in combination with the cytochrome p450c17alpha genotype, estrone and estradiol levels tended to vary by UGT1A1 genotypes. The results presented do not support a strong association between the UGT1A1 promoter polymorphism and the risk of breast cancer.

Adult↗
PubMed2001

Genetic polymorphism of cytochrome P450 3A5 in Chinese.

The CYP3A subfamily enzymes are the most abundant and important drug-metabolizing enzymes. Wide variation in the CYP3A5 expression was well known. Recently, G(-44) to A of CYP3AP1 was found to segregate with CYP3A5*3 defective allele. The homozygous A(-44) subjects showed low expression of CYP3A5. In Caucasian, only 9.2% of CYP3AP1 alleles were with G(-44) and associated with the wild-type CYP3A5*1 allele, which expressed CYP3A5 significantly. By using polymerase chain reaction and FauI endonuclease digestion, we found that 28% of CYP3AP1 alleles are G(-44) in 110 Chinese subjects. The frequency is 3 times higher in Chinese than in Caucasian, implying more Chinese subjects are probably extensive CYP3A5 metabolizers. In two Chinese subjects, we also found a heterozygous G(13048)gt-to-G(13048)gc mutation at the intron 5 splicing donor site, leading to a splicing defect. A 6478-base pair minigene, including intron 4 to intron 7, was used for in vitro transcription. Both the wild-type and the mutated minigenes produced splicing variants. The wild-type minigene used Ggt(13050) as the splicing donor. The mutant minigene used gt(8504) in intron 4 or gt(13112) in intron 5 as the splicing donor for various splicing acceptors. The splicing defect may result in a shorter peptide or cause the frame shift. In the other two Chinese subjects, we found A(14763)-to-G mutation in exon 7, resulting in the Q200R amino acid change. The consequence of the polymorphism site has not been known. In Caucasian, there is a reported T398N polymorphism. In these Chinese subjects, we did not find polymorphism at this site.

China↗
PubMed2002

Genetic polymorphisms in N-acetyltransferase-2 and microsomal epoxide hydrolase, cumulative cigarette smoking, and lung cancer.

N-acetyltrasferase-2 (NAT2) and microsomal epoxide hydrolase (mEH) are polymorphic genes that metabolize different tobacco carcinogens. Smaller studies found inconsistent relationships between NAT2 or mEH polymorphisms and lung cancer risk. To determine whether there is gene-environment interaction between NAT2 polymorphisms, alone or in combination with mEH polymorphisms, and cumulative smoking exposure in the development of lung cancer, we conducted a case control study of 1115 Caucasian lung cancer patients and 1250 spouse and friend controls. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. There was no overall relationship between NAT2 genotype and lung cancer risk; the adjusted odds ratio (OR) of the rapid versus slow acetylator genotypes was 0.96 [95% confidence interval (CI), 0.79-1.16]. However, gene-environment interaction analyses revealed that the adjusted ORs increased significantly as pack-years increased. For nonsmokers, the fitted OR was 0.66 (95% CI, 0.44-0.99), whereas for heavy smokers (80 pack-years), the OR increased to 1.22 (95% CI, 0.89-1.67). When comparing the extreme genotype combinations of the NAT2 rapid acetylator, higher mEH activity genotype to the NAT2 slow acetylator, and very low mEH activity genotype, the corresponding ORs at 0 and 80 pack-years were 0.30 (95% CI, 0.14-0.62) and 2.19 (95% CI, 1.26-3.81), respectively. Results were similar with ORs derived from stratified models. In conclusion, NAT2 rapid acetylator genotypes are protective against lung cancer in nonsmokers but are risk factors in heavy smokers. The joint effects of NAT2 and mEH polymorphisms are consistent with an independent, additive effect of these two genes, modified by smoking history.

Adult↗
PubMed2001

[Genetic polymorphism analysis of apolipoprotein CII microsatellite DNA (TG) n (AG) m in patients with coronary heart disease].

OBJECTIVE: To investigate the relationship between the polymorphism of apolipoprotein CII (apoCII) microsatellite DNA (TG) n (AG) m and coronary heart disease (CHD). METHODS: The apoCII microsatellite DNA (TG) n(AG)m genotypes of 108 patients with CHD and 231 healthy persons were detected by using polymerase chain reaction (PCR) and high voltage denatured polyacrylamid gels electrophoresis. RESULTS: The allele frequency distribution was significantly different between controls and patients with CHD (chi 2 = 19.93, P < 0.05). The allele 17 frequency in CHD group was remarkably higher than that in controls (chi 2 = 13.98, P < 0.01). The concentrations of TG and HDL-C among different genotype groups were significantly different. The levels of TG in 17/29 group and 17/30 group were higher than those in other groups (P < 0.05), while the concentration of HDL-C was lower (P < 0.05). CONCLUSION: The allele 17 of apoCII may be an independent risk factor for CHD in Han population.

Adult↗