Glutathione S-transferase P1 Ile105Val Polymorphism and Oral Cancer Risk: A Meta-Analysis

Objective The glutathione S-transferase P1 (GSTP1) gene has been suggested to play an important role in the pathogenesis of oral cancer. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of GSTP1 Ile105Val polymorphisms with oral cancer risk.Methods Published literature from PubMed and EMBASE were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model.Results 13 studies (1803 oral cancer cases and 2998 controls) for GSTP1 Ile105Val polymorphism were included in the meta-analysis. The results indicated that there was no significant association between GSTP1 Ile105Val polymorphism and oral cancer in the overall population (OR=1.30, 95%CI=0.92-1.38, I²=48.0%, p for heterogeneity=0.027). Further subgroup analysis by ethnicity suggested that GSTP1 Ile105Val polymorphism was significantly associated with oral cancer only in East Asians (OR=1.64, 95%CI=1.16-2.31, I²=0.0%, p for heterogeneity=0.525), but not in Caucasians (OR=1.16, 95%CI=0.73-1.82, I²=7.5%, p for heterogeneity=0.299), Africans (OR=1.10, 95%CI=0.37-3.28), South Asians (OR=1.20, 95%CI=0.69-2.08, I²=74.3%, p for heterogeneity=0.021) and mixed population (OR=0.91, 95%CI=0.70-1.20, I²=39.7%, p for heterogeneity=0.174).Conclusions The present meta-analysis has limited evidence to support the association of GSTP1 Ile105Val polymorphism with HCC risk in the overall population. However, GSTP1 Ile105Val polymorphism might be associated with risk of oral cancer in East Asians.     

Associations of glutathione S-transferase P1, M1, and environmental tobacco smoke with wheezing illness in school children

BACKGROUND: Polymorphisms at the glutathione S-transferase (GST) were associated with asthma-related phenotypes. We hypothesized that the GSTP1 and GSTM1 genotypes could modify the effects of household environmental tobacco smoke (ETS) on childhood wheezing illness. METHODS: We conducted a case-control study comprised of 216 lifetime wheezing children and 185 nonwheezing controls, all of whom were selected from 2524 fourth- to ninth-grade school children in southern Taiwan. RESULTS: Homozygous GSTP1 Ile-105 was significantly associated with current wheezing (OR = 1.78, 95% CI 1.04-3.12), but insignificantly associated with ever wheezing (OR = 1.26, 95% CI 0.82-1.94). The risks of ever or current wheezing on GSTM1 null genotype were positive but not statistically significant. Although household ETS exposure was not associated with wheezing illness, after excluding subjects having in utero ETS or active smoking habits, the adverse effects of household ETS exposure differed significantly by GSTP1-105 genotypes. In children without any ETS exposure at home, GSTP1 Ile-105 homozygosity was significantly related to increased risks for both ever wheezing (OR = 2.29, 95% CI 1.17-4.49) and current wheezing (OR = 4.86, 95% CI 1.86-12.70). In children with household ETS exposure, the risks of wheezing illness did not increase for those carrying two GSTP1 Ile-105 alleles. Children carrying any GSTP1 Val-105 allele were at a significantly greater risk of both ever and current wheezing when exposed to ETS, with a clear dose-response relationship to the number of smokers at home. CONCLUSION: Household ETS exposure is a modifiable cause of wheezing illness in a genetically susceptible subpopulation.     

Association of GSTs gene polymorphisms with treatment outcome of advanced non-small cell lung cancer patients with cisplatin-based chemotherapy

We evaluated the association of GSTM1 null/present, GSTT1 null/present, and GSTP1 IIe105Val polymorphisms with the clinical response to chemotherapy and treatment outcome of NSCLC. Between October 2009 and October 2012, a total of 282 patients with advanced NSCLC were enrolled into our study, and they were followed up until October 2014. The genotypes of GSTM1, GSTT1, and GSTP1 IIe105Val were performed by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By logistic regression analysis, our study found that the Val/Val genotype of GSTP1 IIe105Val was associated with more CR+PR response to chemotherapy when compared with the IIe/IIe genotype, and the OR (95% CI) was 2.18 (1.16-4.12). By multivariate Cox proportional hazards regression analysis, we found the Val/Val genotype of GSTP1 was correlated with lower risk of death in advanced NSCLC (HR, 0.48; 95% CI, 0.25-0.93). However, no association was found between GSTT1 and GSTM1 polymorphisms and response to chemotherapy and overall survival of advanced NSCLC. Moreover, the IIe/Val + Val/Val genotypes of GSTP1 were associated with lower risk of death in never smokers, and the adjusted HR (95% CI) was 0.34 (0.12-0.93). In conclusion, we found that the GSTP1 polymorphism was correlated with better response to chemotherapy and lower risk of death in advanced NSCLC patients.     

Interaction of passive smoking with GST (GSTM1, GSTT1, and GSTP1) genotypes in the risk of cervical cancer in India

Human papilloma virus (HPV) infection is a major cause of cervix cancer, but a number of infected women do not develop invasive lesions, suggesting that HPV infection in itself is not a sufficient factor and that other cofactors, such as smoking, play an important role in development of cervix cancer. Alongside active cigarette smoking, passive smoking is an independent risk factor for cervix cancer. Smoking maintains cervical HPV infection longer and decreases potential of clearing an oncogenic infection. Thus, it is quite possible that polymorphism at detoxifying enzyme coding loci such as GSTM1, GSTT1, and GSTP1 may determine susceptibility to cervix cancer. This study evaluates the combined effects of genetic polymorphisms of GSTM1, GSTT1, and GSTP1 on susceptibility to cervical cancer and interaction of these genes with smoking. On individual analysis of GSTM1, GSTT1, and GSTP1, it was observed that passive smokers having genotypes GSTM1 (null) (OR = 7.0, 95% CI = 2.19-22.36, P = 0.0005), GSTT1 (null) (OR = 10.2, 95% CI = 1.23-84.18, P = 0.02), and GSTP1 (ile/val) (OR = 6.4, 95% CI = 2.25-18.38, P = 0.0005) have an increased risk of developing cervix cancer. It is thus concluded that cervical cancer risk is increased in passive smokers with GSTM1 (null), GSTT1 (null), and GSTP1 (ile/val) genotypes.     

Combined analysis of EPHX1, GSTP1, GSTM1 and GSTT1 gene polymorphisms in relation to chronic obstructive pulmonary disease risk and lung function impairment

Smoking is considered as the major causal factor of chronic obstructive pulmonary disease (COPD). Nevertheless, a minority of chronic heavy cigarette smokers develops COPD. This suggests important contribution of other factors such as genetic predisposing. Our objective was to investigate combined role of EPHX1, GSTP1, M1 and T1 gene polymorphisms in COPD risk, its phenotypes and lung function impairment. Prevalence of EPHX1, GSTP1, M1 and T1 gene polymorphisms were assessed in 234 COPD patients and 182 healthy controls from Tunisia. Genotypes of EPHX1 (Tyr113His; His139Arg) and GSTP1 (Ile105Val; Ala114Val) polymorphisms were performed by PCR-RFLP, while the deletion in GSTM1 and GSTT1 genes was determined using multiplex PCR. Analysis of combinations showed a significant association of 113His/His EPHX1/null-GSTM1 (OR=4.07) and null-GSTM1/105Val/Val GSTP1 (OR =3.56) genotypes with increased risk of COPD (respectively P=0.0094 and P=0.0153). The null-GSTM1/ null-GSTT1, 105Val/Val GSTP1/null GSTT1, 113His/His EPHX1/null-GSTM1 and null-GSTM1/105Val/Val GSTP1 genotypes were related to emphysema (respectively P=0.01; P=0.009; P=0.008 and P=0.001). Combination of 113His/His EPHX1/null-GSTM1 genotypes showed a significant association with the decrease of Δ FEV1 in patients (P =0.028).In conclusion, our results suggest combined EPHX1, GSTP1, GSTM1 and GSTT1 genetic polymorphisms may play a significant role in the development of COPD, emphysema and decline of the lung function.     

Genetic polymorphism of p53, but not GSTP1, is association with susceptibility to esophageal cancer risk - A Meta-Analysis

A number of studies have evaluated two functional polymorphisms on p53 Arg72Pro and GSTP1 Ile105Val, in relation to esophageal cancer susceptibility. However, the results remain conflicting rather than conclusive. This meta-analysis on 2919 cases and 4074 controls for p53 Arg72Pro and 1885 cases and 2194 controls for GSTP1 Ile105Val from 13 published case-control studies showed that no significant general main effects for GSTP1 Ile105Val on esophageal cancer risk. However, we found that the p53 Arg72Pro was associated with an increased risk of esophageal cancer ((Pro/Arg +Pro/Pro) versus Arg/Arg: OR=1.20, 95%CI=1.06-1.36) without any between-study heterogeneity.In the stratified analysis by ethnicity, we found that the increased esophageal cancer risk associated with p53 Arg72Pro polymorphism was more evident in Asian group ((Pro/Arg +Pro/Pro) versus Arg/Arg: OR=1.35, 95%CI=1.14-1.60, P=0.09 for heterogeneity test), although we still failed to find any significant association between GSTP1 Ile105Val polymorphism and esophageal cancer risk in different ethnicity. These results suggest that p53 Arg72Pro polymorphism, but not GSTP1 Ile105Val, may contribute to esophageal cancer development, especially in Asian. Additional well-designed large studies were required for the validation of this association.     

TGFB3 displays parent-of-origin effects among central Europeans with nonsyndromic cleft lip and palate

Mice with a deletion of Tgf-beta3 (-/-) and association studies in humans of different ethnicities support the involvement of TGFB3 in the etiology of orofacial clefts. In this study, we investigated the relevance of TGFB3 in the development of cleft lip and palate (CL/P) among 204 triads of central European origin. Transmission-disequilibrium test (TDT) analysis revealed no significant transmission distortions for each marker alone, and none for any possible haplotypes. However, we found strong evidence for parent-of-origin effects, with lower risk of maternal transmission compared with paternal transmission [I (M) = 0.38; confidence interval (CI): 0.17-0.86] of the risk allele T to an affected offspring at marker rs2300607. This is also expressed in an increased risk of heterozygous children having the T allele inherited from the father (R (P) = 3.47; CI: 1.32-9.11). Our data support the involvement of TGFB3 in the development of oral clefts in patients of central European origin.     

Maternal MTHFR interacts with the offspring's BCL3 genotypes, but not with TGFA, in increasing risk to nonsyndromic cleft lip with or without cleft palate

The 677 C --> T polymorphism in the 5-10 methylenetetrahydrofolate reductase (MTHFR) gene has been associated with nonsyndromic cleft lip with or without cleft palate (CL/P) in some populations, but not others. Previous studies (ie, case-control and transmission disequilibrium tests (TDT)) in Brazilian families with CL/P have been unable to replicate this putative association. However, our group observed a lower proportion of CT heterozygotes among the mothers of CL/P probands, suggesting that the maternal genotype for this polymorphism might influence predisposition to CL/P. In order to further examine this issue, we performed a case-control study of the 677 C --> T/MTHFR polymorphism in families with CL/P ascertained in two regions of Brazil: 172 from S?o Paulo (SP) and 252 from Ceará (CE). The control samples included 243 individuals from SP and 401 from CE. TDT was carried out in 102 patients with CL/P and their parents. No evidence of an association was observed between the 677 C --> T/MTHFR polymorphism and CL/P using the case-control design, while borderline significance was obtained with the TDT (P=0.055). We have also looked for an interaction between maternal MTHFR genotypes and the propositi offspring's genotypes at two candidate susceptibility loci for CL/P, TGFA and BCL3. Interestingly, we observed an interaction between the maternal MTHFR and offspring's BCL3 genotypes (OR: 2.3; 95% CI: 1.1-4.8; P=0.03) but not with the offspring's TGFA genotypes. Therefore, our results reinforce the idea that the maternal MTHFR genotype plays a significant role in susceptibility to CL/P, but its teratogenic effect depends on the genotype of the offspring.     

柳州地区非综合征型唇腭裂环境危险因素1：1病例对照研究

目的探讨柳州地区非综合征型唇腭裂发生的环境危险因素,分析各因素的危险程度。方法采用1：1配对病例对照研究的方法,对广西柳州地区非综合征型唇腭裂患儿进行了环境影响因素的流行病学调查,采用配对资料χ2检验和单因素及多因素条件logistic回归分析筛选出与非综合征型唇腭裂易感性有关的环境因素,使用SPSS13.0进行统计分析。结果共调查非综合征型唇腭裂儿童与正常健康对照儿童178对。非综合征型唇腭裂患儿中单纯唇裂53例,唇裂合并腭裂79例,单纯腭裂46例。多因素分析提示居住在农村（OR=2.35）、母亲孕前6个月或孕早期接触宠物（OR=4.46）、母亲孕前6个月或孕早期被动吸烟（OR=2.20）、先兆流产（OR=20.8）、母亲慢性病史（OR=31.84）、母亲出生缺陷家族史（OR=11.14）、父亲职业有害物理因素接触史（OR=4.62）是非综合征型唇腭裂发生的危险因素,而母亲孕前6个月至孕早期补充叶酸（OR=0.30）、父亲文化程度高（OR=0.14）是非综合征型唇腭裂发生的保护因素。结论影响非综合征型唇腭裂发生的危险因素众多,根据研究结果采取有针对性的健康促进措施,提高孕前保健意识,对降低出生缺陷的发生率将起到积极作用。     

Case-only study of interactions between genetic polymorphisms of GSTM1, P1, T1 and Z1 and smoking in Parkinson's disease

Current opinion contends that complex interactions between genetic and environmental factors play a role in the etiology of Parkinson's disease (PD). Cigarette smoking is thought to reduce risk of PD, and emerging evidence suggests that genetic factors may modulate smoking's effect. We used a case-only design, an approach not previously used to study gene-environment interactions in PD, specifically to study interactions between glutathione-S-transferase (GST) gene polymorphisms and smoking in relation to PD. Four-hundred PD cases (age at onset: 60.0 +/- 10.7 years) were genotyped for common polymorphisms in GSTM1, P1, T1 and Z1 using well-established methods. Smoking exposure data were collected in face-to-face interviews. The independence of the studied GST genotypes and smoking exposure was confirmed by studying 402 healthy, aged individuals. No differences were observed in the distributions of GSTM1, T1 or Z1 polymorphisms between ever-smoked and never-smoked PD cases using logistic regression (all P > 0.43). However, GSTP1 *C haplotypes were over-represented among PD cases who ever smoked (odds ratio for interaction (ORi) = 2.00 (95% CI: 1.11-3.60, P = 0.03)). Analysis revealed that ORi between smoking and the GSTP1-114Val carrier status increased with increasing smoking dose (P = 0.02 for trend). These data suggest that one or more GSTP1 polymorphisms may interact with cigarette smoking to influence the risk for PD.     

Maternal MTR genotype contributes to the risk of non-syndromic cleft lip and palate in the Polish population

The aetiology of non-syndromic cleft lip with or without cleft palate (CL/P) is very complex. It has been shown that polymorphic variants of genes encoding key proteins of folate and methionine metabolism might be important maternal risk factors of having a child with this craniofacial anomaly. Therefore, in our study, mothers with CL/P children as well as control mothers were examined for prevalence of polymorphisms of genes that encode methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1) and reduced folate carrier 1 (RFC1). We observed that there were no statistical differences in allele and genotype frequencies of MTHFR c.677C>T, MTHFD1 c.1958G>A and RFC1 c.80G>A between mothers who had children with CL/P and control mothers. However, mothers with MTR c.2756AG or GG genotype displayed a 2.195-fold increased risk of having a child with CL/P (95% CI 1.189–4.050, p = 0.011). The mechanism by which polymorphic transition of MTR gene might increase the maternal risk of having CL/P progeny is unknown. Our observations are consistent with a significant role of the methyl cycle in the development of craniofacial structures in humans.     

Evidence of the involvement of the DHFR gene in nonsyndromic cleft lip with or without cleft palate

Studies aimed at evidencing genetic causes for neural tube defect (NTD) occurrence have often provided the inspiration for orofacial cleft aetiology investigations. The correlation between the two congenital malformations is provided by the similar incidence timing and the involvement of structures localized in the midline of the embryo. This connection is corroborated by the existence of a number of genes involved in both malformations. In this article, we considered the dihydrofolate reductase (DHFR) gene, previously seen implicated in NTDs, as a candidate for cleft lip with or without cleft palate (CL/P) risk. Four SNPs mapping on the DHFR gene were genotyped for 400 Italian CL/P triads, using TaqMan^® approach. The rs1677693 provided evidence of association, even if at borderline level (P value 0.049). In particular, the variant allele seems to have a protective effect OR = 0.80 (95% C.I. 0.64–0.99). Moreover, the combination of rs1677693(A)-rs1650723(G) alleles showed a significant association OR 0.64 (95% C.I. 0.47–0.86) (P value = 0.006). This represents the first attempt to demonstrate a role for DHFR in CL/P aetiology, howbeit the study of such gene deserves a deepening.     

A functional glutathione S-transferase P1 gene polymorphism is associated with methamphetamine-induced psychosis in Japanese population.

Several lines of evidence suggest that oxidative stress plays a role in the mechanisms of action of methamphetamine (MAP) in the human brain. Given the role of glutathione S-transferases (GSTs) in the protection against oxidative stress, genes encoding the GSTs have been considered as candidates for association studies of MAP abuse. This study was undertaken to investigate the role of the functional polymorphism of GSTP1 gene exon 5 (Ile105Val) in the pathogenesis of MAP abuse. Genotyping for GSTP1 gene polymorphism exon 5 (Ile105Val) in 189 MAP abusers and 199 normal controls was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Association between GSTP1 gene polymorphism and clinical features (prognosis of psychosis (transient-type and prolonged-type), spontaneous relapse (positive and negative), and poly-substance abuse) of MAP abusers was evaluated. Significant differences in the frequency of both alleles (P = 0.026, odds ratio: 1.70, 95% confidence intervals (CI) 1.06-2.72) and genotypes (P = 0.029) between MAP abusers and controls were detected. In particular, a significant difference in both genotype frequency (P = 0.013) and allele frequency (P = 0.014, odds ratio: 1.84, 95% CI 1.13-2.97) between MAP abusers with psychosis (transient-type and prolonged-type) and controls was detected. Our findings suggest that the polymorphism (Ile105Val) on exon 5 of the GSTP1 gene may contribute to a vulnerability to psychosis associated with MAP abuse in Japanese population.     

MSX1 polymorphism associated with risk of oral cleft in Korea: evidence from case-parent trio and case-control studies

Orofacial clefts, including cleft lip with or without palate (CL/P) and cleft palate (CP), are one of the most common congenital malformations in Asian populations, where the rate of incidence is higher than in European or other racial groups. A number of candidate genes have been identified for orofacial clefts, although no single candidate has been consistently identified in all studies. We performed case-parent trio and case- control studies on 6 single nucleotide polymorphisms (SNPs) in the MSX1 gene using a sample of 52 CL/P and CP probands from Korea. In the case-control study, the allele frequencies of 6 MSX1 SNPs were compared between 52 oral cleft cases and 96 unmatched controls. For the case-parent trio study, single-marker and haplotype-based tests of transmission disequilibrium using allelic and genotypic tests revealed significant evidence of linkage in the presence of disequilibrium for 1170 G/A of exon 2. With the GG genotype as a reference group among GG, GA, and AA genotypes at 1170G/A, the disease risk decreased with the presence of the A allele (AA genotype: OR=0.26, 95% CI=0.10-0.99). These results are consistent with evidence from other studies in the US and Chile and confirm the importance of the MSX1 genotype in determining the risk of CL/P and CP in Koreans.     

Relationship between Glutathione S-Transferase P1 Polymorphism and Bronchial Asthma and Atopic Dermatitis

We determined the prevalence of GSTP1-Ile105 and GSTP1-Val105 alleles in patients with bronchial asthma and atopic dermatitis and healthy children of 2 groups (randomized and nonatopic control). The GSTP1-Ile105/Val105 genotype determines the resistance to atopic dermatitis (odds ratio=0.51; 95% confidence interval: 0.28-0.92; p=0.023). However, both homozygotes are at high risk of developing atopic dermatitis (near-significant differences).     

Role of GSTP1 Ile105Val and XRCC1 Arg194Trp,Arg280His and Arg399Gln gene polymorphisms in the clinical outcome of advanced non-small cell lung cancer

We conducted a study to investigate the association between the clinical outcome and GSTP1 Ile105Val and XRCC1 Arg194Trp, Arg280His and Arg399Gln gene polymorphisms in advanced NSCLC patients with cisplatin-based chemotherapy. Between January 2010 and December 2012, a total of 206 patients with advanced NSCLC were histopathologically confirmed were included into analysis. By logistic regression analysis, individuals carrying the AG and GG genotypes of GSTP1 Ile105Val were associated with better response to chemotherapy when compared with the AA genotype, and the adjusted Ors (95% CI) were 2.06 (1.10-3.86) and 4.89 (1.52-18.33), respectively. The TT genotype of XRCC1 Arg194Trp was correlated with better response to chemotherapy compared to the CC genotype, and the adjusted OR (95% CI) was 3.23 (1.20-9.30). By Cox Hazard Proportional Model, the GG genotype of GSTP1 Ile105Val and the TT genotype of XRCC1 Arg194Trp were found to be associated with lower risk of death from all causes when compared with the wide-type genotype, and the adjusted HRs (95% CI) were 0.05 (0.01-0.18) and 0.20 (0.07-0.62), respectively. Moreover, individuals carrying both the G/A+G/G genotype of GSTP1 Ile105Val and the G/A+A/A of XRCC1 Arg194Trp were associated with heavy greater CR+PR response to chemotherapy (OR=2.98, 95% CI=1.39-6.42), and also correlated with longer overall survival of advanced NSCLC (HR=0.19, 95% CI=0.05-0.61). In conclusion, we found that the GSTP1 Ile105Val and XRCC1 Arg194Trp were associated with better response to chemotherapy and longer survival of advanced NSCLC, compared to the wide-type genotype.     

Maternal MTHFR variant forms increase the risk in offspring of isolated nonsyndromic cleft lip with or without cleft palate

The pathogenesis of cleft lip with or without cleft palate (CL/P) is complex; its onset could be due to the interaction of various genetic and environmental factors. Recently MTHFR functional polymorphisms were found to increase the risk of this common malformation; however, this finding is still debated. We investigated 110 sporadic CL/P patients, their parents and 289 unrelated controls for c.665C>T (commonly known as 677C>T; p.Ala222Val) and c.1286A>C (known as 1298A>C; p.Glu429Ala) polymorphism in the MTHFR gene. Transmission disequilibrium test (TDT) showed no distortion in allele transmission. Nevertheless, association studies revealed significant differences in allele frequencies between mothers of CL/P patients and controls. This work supports the hypothesis that a lower MTHFR enzyme activity in pregnant women, mostly related to the c.665C>T variant form, is responsible for a higher risk of having CL/P affected offspring.     

蛋氨酸合酶基因A275 6G位点多态性与非综合征型唇腭裂的关联性研究

目的 研究蛋氨酸合酶基因(methionine synthase,MS)A2756G位点多态性与非综合征型唇腭裂(nonsyndromic cleft lip with or without cleft palate,NSCL/P)的关联性.方法 采用PCR-限制性片段长度多态性技术检测97个NSCL/P病例组核心家庭和104个对照家庭的MS基因A2756G位点的多态性;用人群关联研究分析、病例组核心家庭的传递不平衡检测(transmission disequilibrium test,TDT)、单体型的相对危险度分析(haplotype-based haplotype relative risk,HHRR)、家庭为基础的关联研究(family-based association tests,FBAT)等统计分析.结果 子代、父亲、母亲病例组和对照组之间基因型和等位基因的分布差异均无统计学意义(P>0.05);本研究中在子代和母亲组中未检出GG基因型,AG基因型相对于AA基因型的比值比OR和95%CI分别为子代1.78(0.74～4.34)、父亲0.80(0.36～1.79)、母亲1.26(0.54～2.93),G相对于A基因的OR和95%CI分别为子代1.70(0.78～3.73)、父亲0.88(0.49～1.75)、母亲1.23(0.59～2.60),携带有突变基因G并不能增加患NSCL/P的危险.病例组核心家庭分析,TDT分析χ2=0.034,P>0.05;HHRR分析χ2=0.03,P>0.05;FBAT分析Z=0.186,P>0.05.结论 结果未显示出MS基因A2756G位点多态性和NSCL/P发生的相关性,还待进一步研究.     

Significant association of HLA-B and HLA-DRB1 alleles with cleft lip with or without cleft palate

Nucleotide sequence level typing of HLA-B, -DRB1, and -DPB1 alleles was performed on Japanese patients with cleft lip with or without cleft palate (CL/P). Two HLA-B alleles, B*1501 and B*5101, showed a significant positive association with CL/P. The increase of B*1501 was evident in female patients (OR=3.6, Pc=0.003), whereas the increase of B*5101 was evident in male patients (OR=3.7, Pc < 0.001). One HLA-DRB1 allele, HLA-DRB1*0802 also showed an increase in CL/P patients. Conversely, HLA-B*4403 and DRB1*1302 were not observed in the patient group (Pc=0.01 and Pc=0.02, respectively). No HLA-DPB1 alleles showed significant association with CL/P. Thus, the present study indicates that HLA alleles, or closely linked loci, may be involved in the pathogenesis of CL/P.     

Polymorphisms of the genes encoding the GSTM1, GSTT1 and GSTP1 in Korean women: no association with endometriosis

Endometriosis, one of the most common gynaecologic disorders, shows significantly elevated prevalence in industrial areas and there is also a possible genetic predisposition. Glutathione-S-transferases (GSTs) are enzymes involved in the metabolism of many disease-causing carcinogens and mutagens that are present in human environments. An association between the incidence of endometriosis and the GST genotypes of patients has been suggested. The objective of the present study was to investigate whether the polymorphisms of GSTM1, GSTT1 and GSTP1 are related to endometriosis. Blood samples were available from 259 controls and 194 patients with advanced endometriosis diagnosed by both pathology and laparoscopic findings. The proportion of the GSTM1, GSTT1 and GSTP1 genotypes of the control group were comparable to other populations. There was no significant evidence that the distribution of the GSTM1 and GSTT1 genotype differed between the patients and the controls, with an allelic odds ratio (OR)=1.074 [95% confidence interval (CI)=0.737-1.564] and 1.239 (95% CI = 0.853-1.799), respectively. Also, there was no significant difference in the proportion of GSTP1 genotypes between the women with endometriosis and the control group with the OR = 0.823 (95% CI = 0.536-1.264). The higher risk alleles were contended as GSTM1, GSTT1 null mutation and GSTP1 Ile105Ile polymorphism. There was no significant increase in the risk of endometriosis as the number of higher risk alleles of the GST family increased. In conclusion, our findings suggest that the GSTM1, GSTT1 and GSTP1 genetic polymorphisms are not associated with the development of endometriosis in Korean women.