ABCB1基因C3435T多态性与耐药性癫痫的关系

目的:探讨中国粤西地区汉族人群ABCB1基因C3435T (rs1045642)的单核苷酸多态性与耐药性癫痫的关系.方法:研究对象128例,包括正常对照组60例和癫痫组68例.根据患者对抗癫痫药物的反应性将癫痫组分为耐药组(30例)和药物敏感组(38例).提取所有研究对象外周血基因组DNA,采用PCR扩增后基因测序鉴定ABCB1基因C3435T多态性.测定该位点基因型频率和等位基因频率,并进行统计学分析.结果:各组ABCB1基因C3435T基因型频率的分布符合Hardy-Weinburg平衡,提示其来自同一孟德尔群体.正常对照组与药物敏感组及耐药组,药物敏感组与耐药组间基因型频率比较,差异均无统计学意义(P＞0.05).正常对照组与药物敏感组及耐药组,药物敏感组与耐药组间等位基因型频率比较,差异亦无统计学意义(P＞0.05).结论:本研究结果初步证实ABCB1基因C3435T位点多态性分布与耐药性癫痫之间无相关性.     

COL1A1及IGF-1基因与中国北方汉族人群高度近视相关性研究

目的:探讨I型胶原α1链(collagen I alpha-1,COL1A1)基因和类胰岛素生长因子-1 (insulin-like growth factors-1, IGF-1)基因与中国北方汉族人群高度近视的相关性。方法:收集2011年10月~2017年1月经我院眼科视光学中心诊疗的高度近视眼患者286例(病例组)及正常对照者201例(对照组),病例组按照眼球中轴长度分为A组(眼轴长度≥27 mm)126例和B组(眼轴长度27 mm)160例。用血液基因组DNA提取试剂盒提取受试者外周静脉抗凝血中的基因组DNA,采用多重PCR反应和基因测序得到目标片段COL1A1基因的多态位点rs2075555、rs2075554、rs2269336、rs1107946、rs1007086,IGF-1基因的多态位点rs12423791、rs10860860、rs2946834、rs6214的碱基序列,用卡方检验和Logistic回归分析的方法分析病例组和对照组之间各基因分布的差异。结果:病例组和正常对照组COL1A1基因的单核苷酸多态性位点的基因型频率和等位基因频率均无显著性差异(P0.05)。病例组和正常对照组IGF-1基因的rs12423791位点的基因型频率和等位基因频率有统计学差异(P=0.016),其他3个位点的单核苷酸多态性位点均无显著性差异(P0.05)。病例A组和对照组及A组和B组之间COL1A1基因的5个单核苷酸多态性位点分布均无显著性差异(P0.05),IGF-1基因的rs12423791位点有统计学差异(P=0.033)。结论:胶原类基因COL1A1的多态性与中国北方汉族人群高度近视的发生无显著相关性,IGF-1基因的rs12423791位点的多态性与中国北方汉族人群高度近视的发生有显著相关性。     

2型糖尿病家系患者LEPR基因Gln223Arg多态性的研究

目的:研究黑龙江地区汉族人2型糖尿病家系的LEPR基因Gln223Arg多态性,探讨其与2型糖尿病发病的关系。方法:应用聚合酶链式反应-限制性内切酶长度多态性(PCR-RFLP)技术,对来自于黑龙江地区120个2型糖尿病家系中的210例2型糖尿病患者及319例正常对照的LEPR基因Gln223Arg(668 A→G)位点进行基因分型。结果:LEPR基因Gln223Arg三种基因型在病例组和对照组间整体分布有统计学意义(P=0.034,df=2);除AG基因型(x2=4.550,P<0.01)外,其余各基因型及等位基因在病例组和对照组间分布未见显著性差异(P>0.05)。结论:LEPR基因Gln223Arg多态性与黑龙江地区汉族人2型糖尿病有关,LEPR基因可能为中国人2型糖尿病发病的相关易感基因。     

CYP1A1基因单核苷酸多态性与肺癌的相关性研究

目的:探讨代谢酶CYP1A1基因MspI位点多态性与新疆汉族人群肺癌遗传易感性之间的相关性.方法:应用聚合酶链式反应(PCR)-限制性片段长度多态性(RFLP)技术检测59例新疆汉族肺癌和84例新疆汉族健康人的CYP1A1基因MspI位点多态性分布频率,并分析了CYP1A1基因MspI位点多态性与新疆汉族人群肺癌遗传易感性和患者性别之间的相关性.结果:(1)CYP1A1基因MspI位点3种多态基因型分布频率在两组间比较差异有统计学意义(χ2=6.682,P=0.035),CC基因型在病例组的分布频率显著高于正常对照组.(2)携带突变CC基因型的个体较携带TT基因型的个体患肺癌的危险性增加(OR=3.759.95%CI=1.228-11.494,P=0.035).(3)男女肺癌患者的CYP1A1基因MspI位点基因型及等位基因频率的差异均无显著性(P>0.05).结论:(1)CC突变基因型可能是新疆汉族人群的肺癌易感因素.(2)CYP1A1基因MspI位点多态性可能与新疆汉族肺癌患者的性别无关.     

CISH基因多态性与结核病易感性的相关性研究

目的:寻找肺结核的易感位点,探索宿主遗传因素差异对肺结核发病的影响,为肺结核的预防和药物研发提供理论依据。方法:对1218名汉族居民进行病例对照研究,其中病例组600例,对照组618例,进行流行病学调查和生化指标检查。运用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术检测CISH基因rs2239751和rs622502的基因型分布,探讨CISH基因多态性与中国汉族人群肺结核易感性的关联性。结果:CISH基因的rs2239751和rs622502等位基因分布均符合Hardy-Weinberg(H-W)遗传平衡定律(P0.05)。rs2239751位点基因型和等位基因分布在两组间差异有统计学意义,P值分别为0.013和0.01,并且携带C等位基因个体患肺结核的风险是携带A等位基因的个体1.16倍(95%CI=1.03-1.29,P=0.01)。rs2239751基因分型结果在女性病例组和对照组中差异有统计学意义,P值为0.007,OR(95%CI)为1.51(1.12-2.03)。rs2239751基因分型结果在45岁人群病例组和对照组中差异有统计学意义,P值为0.010,OR(95%CI)为1.32(1.07-1.64)。rs622502位点基因型和等位基因分布在两组间差异均无统计学意义(P0.05)。结论:在汉族人群中,rs2239751位点多态性可能是肺结核的危险因素之一,C等位基因为风险等位基因。rs2239751基因多态性与肺结核的关联性仅限于于女性和45岁人群。rs622502位点多态性可能与肺结核无关。     

新疆维吾尔族、汉族阿尔茨海默病Neprilysin基因单核苷酸多态性研究

摘要目的：探讨新疆地区维吾尔族、汉族脑啡肽酶（Neprilysin,NEP）基因单核苷酸多态性与阿尔茨海默病（Alzheimer’SdiseaseAD）的关系。方法：对新疆地区维吾尔族、汉族≥50岁8284名人群进行AD流行病学调查,参照ADRDA．NINCDS的标准,选取散发性阿尔茨海默病（sporadicAlzheimer’s disease,SAD）患者209例（AD组）与正常对照220例（对照组）,应用聚合酶链反应一限制性片段长度多态性技术（PCR）检测NEP基因多态性,采用病例一对照的关联分析方法对NEP基因rs3736187位点进行基因型和等位基因频率分析。结果：（1）新疆维吾尔族、汉族两民族AD组与对照组间NEP基因基因型频率和等位基因频率分布差异均有统计学意义（P〈0．05）。携带T等位基因个体出现AD的危险性高于携带c等位基因的个体（0R=1．981,P〈0．05）。（2）新疆维吾尔族、汉族不同民族之间比较NEP基因基因型频率和等位基因频率分布差异均无统计学意义（P〉0．05）,而在同一民族中AD组和对照组之间比较NEP基因等位基因频率分布差异均具有统计学意义（P〈0．05）。（3）两个年龄分段（〈65岁及≥65岁）之间NEP基因基因型频率和等位基因频率分布差异均无统计学意义（P〉0．05）,而在同一年龄段内部AD组与对照组间等位基因频率分布差异具有统计学意义（P〈0．05）。（4）男性、女性之间NEP基因基因型频率和等位基因频率分布差异均无统计学意义,而在女性AD组与对照组间等位基因频率分布差异有统计学意义（P〈0．05）。结论：NEP基因rs3736187位点基因型频率和等位基因频率在新疆维吾尔族、汉族两民族间的分布相似;NEP基因的T等位基因是SAD的危险因素,在新疆维吾尔族、汉族两民族及女性SAD的发病中起重要作用。     

雌激素受体α(ESR1)基因PvuⅡ和XbaⅠ位点基因多态性与HBV慢性感染的相关性研究

目的:探讨雌激素受体ESR1(Estrogen Receptor alpha gene)基因的PvuⅡ(rs2234693)和XbaⅠ (rs9340799)两个单核苷酸多态性(single nucleotide polymorphisms, SNPs)位点的基因多态性与乙型肝炎病毒HBV(Hepatitis B Virus)慢性感染的相关性,为控制HBV持续感染提供新的思路和科学依据。方法:选择107例慢性乙型病毒性肝炎患者为病例组及107例同期体检的健康人群为对照组,基于高分辨熔解曲线技术(High Resolution Melting,HRM)建立PCR-HRM分子诊断方法,检测其雌激素受体ESR1基因两个SNP位点rs2234693(TC)和rs9340799(AG)的基因多态性,并通过基因测序进一步验证,探讨上述两个SNP位点与HBV慢性感染的相关性。结果:病例组和健康对照组ESR1基因rs2234693(TC)位点的基因型频率比较差异具有统计学意义(P0.05),而两组间rs2234693位点等位基因频率比较差异没有统计学意义(P0.05);病例组和健康对照组间ESR1基因rs9340799(AG)位点的各基因型频率差异具有统计学意义(P0.05),慢性乙肝病例组GG基因型明显升高,两组间rs9340799位点等位基因频率差异亦具有统计学意义(P0.05)。Logistic回归分析显示rs9340799位点的G基因可增加HBV慢性感染的发病风险,A基因可降低HBV慢性感染的发病风险。结论:雌激素受体基因ESR1的rs9340799 (AG)位点的GG基因型和G等位基因可能是HBV感染慢性化的遗传易感基因,GG基因型与HBV的慢性感染具有一定的相关性。     

BRCA1 基因启动子区SNPs 与散发性乳腺癌易感性的相关研究

目的:探讨BRCA1基因启动子区rs11655505、rs73625095位点单核苷酸多态性与散发性乳腺癌易感性的关系。方法:采用ASA-PCR方法对200例乳腺癌患者(均经病理确诊)及200例正常女性BRCA1基因启动子区rs11655505(A/G)、rs73625095(A/G)位点单核苷酸多态性(SNP)进行分析,并将其PCR产物进行测序。结果:乳腺癌患者BRCA1基因启动子区rs11655505位点的A/G基因型频率为75%,显著高于正常人的40%;A/A基因型频率为7%,G/G基因型频率为18%,分别低于正常人的30%、30%。此位点的A或G等位基因在乳腺癌病例组及对照组中均无差别(x2=2.427,P=0.119);rs73625095位点的A/G基因型频率为68%,显著高于正常人的15%;G/G基因型频率为32%,低于正常人的84%;乳腺癌病例组中BRCA1基因启动子区rs11655505、rs73625095位点的A/G基因型与淋巴结转移与否相比,差别均有统计学意义(x2=7.321,P=0.026、x2=4.782,P=0.029)。结论:BRCA1基因rs11655505位点、rs736...     

TGF-β1基因rs200482214位点多态性与黑龙江省汉族人群慢性牙周炎的相关性研究

目的:探讨转移生长因子β1(transforminggrowth factor beta-l,TGF-β1)位点rs200482214基因多态性与黑龙江省汉族人群慢性牙周炎的易感性的相关性。方法:选取2012年3月至2013年7月在哈尔滨医科大学附属口腔医院牙周科就诊的135例轻、中、重度慢性牙周炎汉族患者(牙周炎组)和108例汉族健康对照者(健康对照组)作为研究对象,基因组DNA来自口腔颊粘膜拭子,采用多重单碱基延伸SNP分型技术(Multiplex SNaPshot technique)对所有受试者TGF-β1基因rs200482214位点进行检测,比较两组间此位点基因型分布和等位基因频率的差异。结果:(1)TGF-β1基因rs200482214位点各基因型(GG、GA、AA)分布均符合Hardy-Weinberg遗传平衡定律(P0.05);(2)TGF-β1基因rs200482214位点GG、GA、AA在牙周炎组和健康对照组的分布频率分别为61.5%、30.4%、8.1%和63.0%、28.7%、8.3%,两组人群基因型分布频率差异无统计学意义(P0.05);等位基因G、A在牙周炎组和健康对照组分布频率分别为76.7%、23.3%和77.3%、22.7%,两组人群的等位基因分布频率差异亦无统计学意义(P0.05)。结论:TGF-β1位点rs200482214基因多态性与黑龙江省汉族人群慢性牙周炎的易感性不具有相关性。     

2型糖尿病家系患者LEPR基因Gln223Arg多态性的研究

目的：研究黑龙江地区汉族人2型糖尿病家系的LEPR基因Gln223Arg多态性,探讨其与2型糖尿病发病的关系。方法：应用聚合酶链式反应-限制性内切酶长度多态性（PCR-RFLP）技术,对来自于黑龙江地区120个2型糖尿病家系中的210例2型糖尿病患者及319例正常对照的LEPR基因Gln223Arg（668 A→G）位点进行基因分型。结果：LEPR基因Gln223Arg三种基因型在病例组和对照组间整体分布有统计学意义（P=0.034,df=2）;除AG基因型（x2=4.550,P〈0.01）外,其余各基因型及等位基因在病例组和对照组间分布未见显著性差异（P〉0.05）。结论：LEPR基因Gln223Arg多态性与黑龙江地区汉族人2型糖尿病有关,LEPR基因可能为中国人2型糖尿病发病的相关易感基因。     

SULT1A1 Arg213His polymorphism, smoked meat, and breast cancer risk: a case-control study and meta-analysis

SULT1A1 is involved in both detoxification of estrogens and bioactivation of carcinogens in smoked meat. SULT1A1 Arg213His polymorphism's effect on breast cancer risk is still unclear. We recruited 400 case-control pairs to investigate the association between SULT1A1 genotypes and breast cancer risk, and the combined effect of SULT1A1 polymorphism and daily intake of smoked meat. Participants were questioned about their dietary habits and other risk factors, and their SULT1A1 genotypes were determined. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated by multivariable unconditional logistic regression. We also performed a meta-analysis of relevant published studies to test these associations. In the case-control study, no significant associations were observed between SULT1A1 polymorphism and breast cancer risk. In the meta-analysis, SULT1A1 His/His genotype slightly increased risk among both overall and postmenopausal women (OR(pooled-overall)=1.12, 95% CI: 1.02-1.24; OR(pooled-post)=1.17, 95% CI: 1.03-1.32). A larger positive association was observed in Asian populations (OR(pooled-Asian)=2.01, 95% CI: 1.24-3.26). In our case-control study, high energy-adjusted daily intake of smoked meat was significantly associated with breast cancer risk in overall, pre- and postmenopausal women (aORs: 2.31-3.13, OR 95% CIs exclude 1). High smoked meat intake interacted positively with the His variant allele (all γ>1). These results correlated with those of the meta-analysis (γ(pooled-overall)=1.27). The SULT1A1 His/His genotype may increase the risk of breast cancer among Asian women, and dietary exposure to heterocyclic amines and polycyclic aromatic hydrocarbons, along with the SULT1A1 His/His variant genotype, may synergistically increase the risk of breast cancer.     

An investigation of the relationship between SULT1A1 Arg213His polymorphism and lung cancer susceptibility in a Turkish population

Human sulfotransferase 1A1 (SULT1A1), the most expressed isoform of the phenol SULT1 subfamily, is an important member of sulfotransferase superfamily. A transition, G to A at position 638, in SULT1A1 gene, results in Arg²¹³His change. This single nucleotide polymorphism reduces the activity and thermostability of SULT1A1 enzyme. Thus, in the present study the relationship between SULT1A1 Arg²¹³His polymorphism and lung cancer was investigated. One hundred and six case and 271 control samples were studied using PCR‐RFLP. There was no significant difference in genotype and allele distribution between lung cancer and control populations (p = 0.07; p = 0.06, respectively). Compared with the SULT1A1*1/SULT1A1*1 genotype the variant SULT1A1 genotype (SULT1A1*1/SULT1A1*2 or SULT1A1*2/SULT1A1*2) was associated with a significantly increased lung cancer risk in cases (p = 0.027). In male populations, there was no significant difference between case and controls (p = 0.313). In female populations, however, this difference was found to be significant (p = 0.04). In smoker and non‐smoker populations, no significant relationship was evident between lung cancer and control population (p = 0.170, p = 0.065, respectively). Statistical analyses of histological types of lung cancer in comparison with the control individuals indicated a significant difference between SULT1A1 Arg²¹³His polymorphism and SCC (p = 0.027) and other types of cancer (p = 0.037), except SMCC (p = 0.854). Copyright © 2009 John Wiley & Sons, Ltd.     

SULT1A1 Arg213His polymorphism and susceptibility of environment-related cancers: a meta analysis of 5,915 cases and 7,900 controls

The common genetic polymorphism for SULT1A1 is Arg213His polymorphism, which may affect the sulfation process of various environmental carcinogens and thus is suggested to be related to susceptibility of several cancers. However, studies on the association between SULT1A1 Arg213His polymorphism and cancer susceptibility are inconsistent. To assess the relationship between Arg213His polymorphism and environmental-related cancers systematically, we performed a meta analysis from 20 case–control studies including 5,915 cases and 7,900 controls. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of risk, we found a significant association between SULT1A1 Arg213His polymorphism and environment-related cancers (for dominant model: OR 1.22, 95% CI 1.07–1.39, P = 0.003). When stratified by ethnicity, a significant risk was observed in Asian cases, compared with controls (for dominant model: OR 1.69, 95% CI 1.17–2.43, P = 0.005). When we chose only smokers in our analysis, we also found a significantly increased risk between Arg213His polymorphism and susceptibility of environment-related cancers for participants exposed to a smoking environment. In conclusion, SULT1A1 Arg213His polymorphism, ethnicity, smoking may modulate environment-related cancer risk. Studies on gene–gene interactions in the sequential or concurrent metabolic pathway and gene-environment interactions need to be further conducted to explore the susceptibility of cancer occurrence.     

Association of SULT1A1 and UGT1A1 polymorphisms with breast cancer risk and phenotypes in Russian women

Estrogens are critical for breast cancer initiation and development. Sulfotransferase 1A1 (SULT1A1) and UDP-glucuronosyltransferase 1A1 (UGT1A1) conjugate and inactivate both estrogens and their metabolites, thus preventing estrogen-mediated mitosis and mutagenesis. SULT1A1 and UGT1A1 are both polymorphic, and different alleles encode functionally different allozymes. We hypothesize that low-activity alleles SULT1A1*2 and UGT1A1*28 are associated with higher risk for breast cancer and more severe breast tumor phenotypes. We performed a case-control study, which included 119 women of Russian ancestry with breast cancer and 121 age-matched Russian female controls. We used PCR followed by pyrosequencing to determine the SULT1A1 and UGT1A1 genotypes. Allele UGT1A1*28 was present at a higher frequency than the wild-type UGT1A1*1 allele in breast cancer patients as compared to controls (P = 0.002, OR = 1.79, CI 1.23–2.63). Consistently, the frequency of genotypes that contain allele UGT1A1*28 in the homozygous or the heterozygous state was greater in breast cancer patients as compared with the frequency of the wild-type UGT1A1*1/*1 genotype (P = 0.003, OR = 4.00, CI 1.49–11.11 and P = 0.014, OR = 2.04, CI 1.14–3.57, respectively). Individuals carrying allele UGT1A1*28 in the homo-or heterozygous state had larger breast tumors (>2 cm) as compared to the group with high-activity genotypes (P = 0.011, IR = 3.44, CI 1.42–8.36). No association was observed between any of the SULT1A1 genotypes and breast cancer risk or phenotypes. Our data suggest that UGT1A1, but not SULT1A1, genotypes are important for breast cancer risk and phenotype in Russian women. Published in Russian in Molekulyarnaya Biologiya, 2006, Vol. 40, No. 2, pp. 263–270. The article was translated by the authors.     

Association of polymorphisms in SULT1A1 and UGT1A1 Genes with breast cancer risk and phenotypes in Russian women

Estrogens are critical for breast cancer initiation and development. Sulfotransferase 1A1 (SULT1A1) and UDP-glucuronosyltransferase 1A1 (UGT1A1) conjugate and inactivate both estrogens and their metabolites, thus preventing estrogen-mediated mitosis and mutagenesis. SULT1A1 and UGT1A1 genes are both polymorphic, and different alleles encode functionally different allozymes. We hypothesize that low activity alleles SULT1A1*2 and UGT1A1*28 are associated with the higher risk for breast cancer and more severe breast tumor phenotypes. We performed a case-control study, which included 119 women of Russian ancestry with breast cancer and 121 age-matched Russian female controls. We used PCR, followed by pyrosequencing to determine SULT1A1 and UGT1A1 genotypes. Our data showed that UGT1A1*28 allele was presented at a higher frequency than the wild type UGT1A1*1 allele in breast cancer patients as compared to controls (p = 0.002, OR = 1.79, CI 1.23-2.63). Consistently, the frequency of genotypes that contain the UGT1A1*28 allele in the homozygous or heterozygous state was greater than the frequency of the wild type UGT1A1*1/*1 genotype in breast cancer patients as compared to controls (p = 0.003, OR = 4.00, CI 1.49-11.11 and p = 0.014, OR = 2.04, CI 1.14-3.57, respectively). The group of individuals, carrying the UGT1A1*28 allele in the homo- or heterozygous state also presented larger breast tumors (>2 cm) as compared to the group with high enzymatic activity genotypes p = 0.011, OR = 3.44, CI 1.42-8.36). No association was observed between any of the SULT1A1 genotypes and breast cancer risk or phenotypes. Our data suggest that UGT1A1 but not SULT1A1 genotype might be important for breast cancer risk and phenotype in Russian women.     

XRCC1 Arg399Gln was associated with repair capacity for DNA damage induced by occupational chromium exposure

ABSTRACT: BACKGROUND: Occupational chromium exposure may induce DNA damage and lead to lung cancer and other work-related diseases. DNA repair gene polymorphisms, which may alter the efficiency of DNA repair, thus may contribute to genetic susceptibility of DNA damage. The aim of this study was to test the hypothesis that the genetic variations of 9 major DNA repair genes could modulate the hexavalent chromium (Cr (VI))-induced DNA damage. FINDINGS: The median (P25-P75) of Olive tail moment was 0.93 (0.58-1.79) for individuals carrying GG genotype of XRCC1 Arg399Gln (G/A), 0.73 (0.46-1.35) for GA heterozygote and 0.50 (0.43-0.93) for AA genotype. Significant difference was found among the subjects with three different genotypes (P = 0.048) after adjusting the confounding factors. The median of Olive tail moment of the subjects carrying A allele (the genotypes of AA and GA) was 0.66 (0.44-1.31), which was significantly lower than that of subjects with GG genotype (P = 0.043). The A allele conferred a significantly reduced risk of DNA damage with the OR of 0.39 (95% CI: 0.15-0.99, P = 0.048). No significant association was found between the XRCC1Arg194Trp, ERCC1 C8092A, ERCC5 His1104Asp, ERCC6 Gly399Asp, GSTP1 Ile105Val, OGG1 Ser326Cys, XPC Lys939Gln, XPD Lys751Gln and DNA damage. CONCLUSION: The polymorphism of Arg399Gln in XRCC1 was associated with the Cr (VI)- induced DNA damage. XRCC1 Arg399Gln may serve as a genetic biomarker of susceptibility for Cr (VI)- induced DNA damage.     

Genetic Polymorphisms of Sulfotransferases (SULT1A1 and SULT1A2) in a Turkish Population

Sulfotransferases (SULTs) play a significant role in the biotransformation of a variety of xenobiotics and endogenous compounds. SULTs are genetically polymorphic enzymes; to date, 12 human cytosolic SULT isoforms have been identified. This study investigated SULT1A1 and SULT1A2 gene polymorphism using a PCR-RFLP method (n = 303). The frequency of the SULT1A1*1 allele was 76.2% and SULT1A1*2 was 23.8%. The SULT1A1*3 allele could not be identified. The SULT1A2 frequencies were 69.2% (SULT1A2*1), 18.3% (SULT1A2*2), and 12.5% (SULT1A2*3). The SULT1A1 and SULT1A2 loci were in Hardy-Weinberg equilibrium (SULT1A1 χ2 = 0.58, P = 0.44; SULT1A2 χ2 = 7.28, P = 0.06). Linkage analysis indicated a close linkage between these two genes (χ2 = 5.31, P < 0.01); therefore, the statistical hypothesis that SULT1A1 and SULT1A2 alleles are independently distributed was rejected. Additionally, a strongly positive linkage was detected between SULT1A1*2 and SULT1A2*2 alleles in this population (D' = 0.79, χ2 = 33.33).     

The XRCC1 Arg280His polymorphism contributes to cancer susceptibility: an update by meta-analysis of 53 individual studies

The X-ray repair cross-complementing group 1 (XRCC1) protein plays a central role in DNA repair pathways. Epidemiological studies have revealed the association between XRCC1 Arg280His polymorphism and cancer risk, but the results were inconsistent. We conducted this meta-analysis to assess the effect of XRCC1 Arg280His polymorphism on cancer susceptibility with accumulated data. Up to January 2012, 53 case‐control studies with 21,349 cases and 23,649 controls were available for our study. Summary odds ratios (OR) and corresponding 95% confidence intervals (CIs) for XRCC1 Arg280His polymorphism and cancer were estimated using fixed‐ or random-effects models when appropriate. Our meta-analysis identified that elevated cancer risk was statistically associated with the minor variant His allele and Arg–His/His–His genotypes both in the overall population (allele comparison, His versus Arg: OR = 1.16; 95% CI: 1.08–1.25; dominant comparison, Arg–His/His–His versus Arg–Arg: OR = 1.17; 95% CI: 1.08–1.27) and in terms of subgroup analyses by ethnicity for both Caucasians and non‐Caucasians. However, no significant result was observed in the stratified analysis by cancer type. Moreover, significantly increased cancer risk was observed in smokers. These findings indicated that XRCC1 Arg280His polymorphism may play a role in cancer development.     

Sulfating-activity and stability of cDNA-expressed allozymes of human phenol sulfotransferase, ST1A3*1 ((213)Arg) and ST1A3*2 ((213)His), both of which exist in Japanese as well as Caucasians.

We recently found single amino acid substitutions ((213)Arg/His and (223)Met/Val) in polymorphic human phenol-sulfating phenol sulfotransferase (SULT: cDNAs encoding ST1A3, P PST or HAST1/2) among Caucasians and African-Americans. In a Japanese population (n = 143), allele frequencies of (213)Arg and (213)His were 83.2 and 16. 8%, respectively, but the (223)Val allele was not found. (213)His homozygosity was reportedly associated with both very low (>7-fold) sulfating activities of p-nitrophenol (at 4 microM) and low thermostability in platelets. Sulfating-activity determinations using recombinant (213)Arg- and (213)His-forms (ST1A3*1 and ST1A3*2, respectively) did not, however, reveal appreciable deficiency in [(35)S]3'-phosphoadenosine 5'-phosphosulfate (PAPS)-dependent sulfation of p-nitrophenol (4 microM) by ST1A3*2 (7.5 vs. 10.2 nmol/min/nmol SULT for ST1A3). Kinetic parameters for p-nitrophenol for p-nitrophenol sulfation supported the slight decrease in sulfating activities at 4 microM (K(m), 0.82 vs. 1.75 microM; V(max), 13.2 vs. 13.1 nmol/min/nmol SULT, respectively, for ST1A3*1 and *2). p-Nitrophenyl sulfate-dependent 2-naphthol sulfation by ST1A3*2 was 69% of that by ST1A3*1 (p<0.05). However, ST1A3*2 was remarkably unstable at 45 and 37 degrees C as compared to ST1A3*1. The lower p-nitrophenol sulfating activity of ST1A3*2 may explain the lower platelet p-nitrophenol sulfation in ST1A3*2 homozygotes. Protein instability and ST1A3 gene regulation may be both involved in the polymorphism of p-nitrophenol sulfation in human tissues.     

Sulfotransferase SULT1A1 Arg213His Polymorphism with Cancer Risk: A Meta-Analysis of 53 Case-Control Studies

Background

The SULT1A1 Arg213His (rs9282861) polymorphism is reported to be associated with many kinds of cancer risk. However, the findings are conflicting. For better understanding this SNP site and cancer risk, we summarized available data and performed this meta-analysis.

Methods

Data were collected from the following electronic databases: PubMed, Web of Knowledge and CNKI. The association was assessed by odd ratio (OR) and the corresponding 95% confidence interval (95% CI).

Results

A total of 53 studies including 16733 cancer patients and 23334 controls based on the search criteria were analyzed. Overall, we found SULT1A1 Arg213His polymorphism can increase cancer risk under heterozygous (OR = 1.09, 95% CI = 1.01–1.18, P = 0.040), dominant (OR = 1.10, 95% CI = 1.01–1.19, P = 0.021) and allelic (OR = 1.08, 95% CI = 1.02–1.16, P = 0.015) models. In subgroup analyses, significant associations were observed in upper aero digestive tract (UADT) cancer (heterozygous model: OR = 1.62, 95% CI = 1.11–2.35, P = 0.012; dominant model: OR = 1.63, 95% CI = 1.13–2.35, P = 0.009; allelic model: OR = 1.52, 95% CI = 1.10–2.11, P = 0.012) and Indians (recessive model: OR = 1.93, 95% CI = 1.22–3.07, P = 0.005) subgroups. Hospital based study also showed marginally significant association. In the breast cancer subgroup, ethnicity and publication year revealed by meta-regression analysis and one study found by sensitivity analysis were the main sources of heterogeneity. The association between SULT1A1 Arg213His and breast cancer risk was not significant. No publication bias was detected.

Conclusions

The present meta-analysis suggests that SULT1A1 Arg213His polymorphism plays an important role in carcinogenesis, which may be a genetic factor affecting individual susceptibility to UADT cancer. SULT1A1 Arg213His didn''t show any association with breast cancer, but the possible risk in Asian population needs further investigation.