RBP4多态性与2型糖尿病患者的相关性研究

目的 探讨视黄醛结合蛋白(RBP4)基因多态性在苏州地区汉族人群中的频率分布及其与2型糖尿病(T2DM)的相关性.方法 采用TaqMan探针基因分型技术结合琼脂糖凝胶电泳技术,检测384例T2DM患者和384例健康人RBP4的多态性,同时测定其空腹血糖(FBG)、总胆固醇(TC)、三酰甘油(TG)水平.结果 T2DM组和对照组RBP4-803,G>A; 5169,C>T; 6969,G>C 3个单核苷酸多态性(SNP)位点的基因型频率和等位基因频率分布的差异无统计学意义(P>0.05).经Logistic回归分析,校正年龄、性别、体质指数等因素影响后,各位点基因型相对风险分析未发现与T2DM发生有关的基因型,而且通过年龄、性别、高血压病史、TG、TC进行的分层分析,也未发现各基因型之间发生T2DM风险的差异性.单倍体表型分析也未发现与T2DM有关的单倍型.结论 RBP4 -803,G>A; 5169,C>T; 6969,G>C多态性与中国苏州地区T2DM的发生无关.     

RBP4与FOXO1基因单核苷酸多态性与2型糖尿病的相关性研究

Objective To investigate the distribution of single nucleotide polymorphisms(SNPs) on retinol binding protein 4(RBP4) genes and forkhead box O1 (FOXO1) gene, and their relationships with the occurrence of type Ⅱ diabetes mellitus (T2DM) in Chinese Han population. Methods Totally ten SNPs on RBP4 and FOXO1 were determined in 384 T2DM patients and 384 normal controls by TaqMan probe genotyping and agarose gel electrophoresis methods. And their serum level of fasting blood glucose (FBG), total cholesterol (TC) and trigly- ceride (TG) were also estimated. Results For RBP4, there was no significance for various genetypes and alleles including - 803 G > A, + 5169 C > T, and + 6969 G > C between two groups (P > 0.05). Each genotype had no relationships with T2DM (using adjusted logistic regression models). No haplotype was associated with T2DM. For FOXO1, among seven SNPs typed, significant variation was found in the frequency distribution of rs7324943 G/T in the two groups(χ2=4.02, P = 0.044), and further stratification analysis showed that in subjects of aged 40 and non-hypertension, there was a higher risk of T2DM in GT heterozygous carriers than in GG homozygous carriers (OR = 1.47, 1.80), T allele carriers showed higher risk than non-T carriers (OR = 1.42,1.79). For rs17592236 C/T, though no significant frequency variation was found between two groups (χ2 = 0.39, P = 0.401), but in subjects of aged ≤ 40, stratification analysis showed dramatically increased risk of T2DM in CT and TT carriers than in CC carriers (OR = 6.33,10.15), T allele carriers showed 7. 11-fold higher risk than non-T carriers. A haplotype CT related to T2DM susceptibility was also found, which could decrease the risk of its carriers by 28%. Conclusions For BBP4, the polymorphisms of - 803 G > A, + 5169 C > T, and + 6969 G > C had no relationships with T2DM in Chinese Han population. For FOXO1, the polymorphism of rs7324943 G/T,rs17592236 C/T and a haplotype CT were found related to the susceptibility of T2DM in Chinese Han population. Yet further studies are necessary to explain the impact of these polymorphisms on the disease occurrence.     

LOX-1基因501G>C和IVS4-73C>T多态性与湖南汉族人不稳定型心绞痛发病的相关性

目的:研究血凝素样氧化性低密度脂蛋白受体-1(LOX-1)基因501G>C和IVS4-73C>T多态性与不稳定型心绞痛(UAP)发病的相关性.方法:运用PCR-RFLP检测LOX-1基因501G>C和IVS4-73C>T单核苷酸多态性(SNP)住点基因型,观察其多态性的基因型及等位基因在150例湖南籍汉族人UAP患者和146例健康对照中的分布频率.结果:病例组和对照组的LOX-1 501G>C基因型和等位基因频率分布差异无统计学意义(P=0.248和P=0.109).含有突变基因的(GC+CC)基因型与野生型GG基因型的频率分布差异无统计学意义(OR=0.671,P=0.131):LOX-1 IVS4-73C>T基因型和等位基因频率分布差异无统计学意义(P=0.756和P=0.559),含有突变基因的(CT+TT)基因型与野生型CC基因型的频率分布差异亦无统计学意义(OR=0.886,P=0.692).结论:湖南汉族人群中LOX-1 501G>C和IVS4-73C>T多态性与UAP发病无明显相关性.     

广西壮族人群ADIPOQ基因rs2241766T/G多态性与T2DM易感性的相关性分析

摘要:目的探讨脂联素基因(ADIPOQ)rs2241766T/G位点单核苷酸多态性(SNP)与广西壮族人群新发2型糖尿病(T2DM)易感性及不同代谢参数之间的相关性。方法采用 SNPscan高通量技术检测广西地区212例新发T2DM患者和289例健康人对照者的rs2241766T/G基因分型,统计并分析二者的差异性。结果rs2241766T/G 位点存在GG、TG和TT基因型及G和T等位基因;T2DM组与对照组基因型频率差异有统计学意义(X = 6.294,P = 0.043) ;TG( OR= 2.443, 95%CI:1.197-4.988 ,P=0.014)、TT( OR= 2.057 ,95%CI:1.017-4.159, P=0.045)及TG+TT( OR= 2.222, 95%CI:1.122~4.402 ,P=0.022)基因型与T2DM风险增加显著相关;在调整性别和年龄共同混杂因素后,TG .TT和TG+TT基因型患T2DM风险分别是GG基因型的2.863倍 ( OR= 2.863 ,95% CI:1.352~ 6.060,P=0.006)、2.291倍(OR=2.291, 95%Cl:1.094~4.800, P=0.028)和2.532 倍(OR= 2.532,95%CI:1.235~ 5.192 ,P=0.011);与健康人对照组比较,不同基因型T2DM患者的多种临床生化代谢指标间的差异有统计学意义(P均<0.05),且证实rs2241766T/G SNP可影响患者肌酐(Gr)水平(P=0.049)。结论ADIPOQ rs2241766T/G SNP与广西壮族人群T2DM易感性增加相关,或可作为预测T2DM风险的潜在遺传标志物。     

Cnb1基因多态性与2型糖尿病相关性研究

目的:研究Cnb1基因的单核苷酸多态性(SNPs)在上海地区人群2型糖尿病(2-DM)患者和正常对照组人群中的基因型频率、等位基因频率分布及其与2-DM的相关性。方法:选取上海地区无亲缘关系的2-DM患者447例及正常对照440名。用稳态模式胰岛素抵抗指数(HOMA-R)及胰岛β细胞功能指数(HOMA-β)估测外周组织胰岛素敏感度及胰岛β细胞功能。采用等位基因专一性实时PCR技术,对2-DM患者及正常对照组人群Cnb1基因的5个SNP位点rs12329083、rs12465425、rs13029910、rs2861814及rs11692815进行基因分型;并进行统计学分析,研究这些位点与2-DM的相关性。结果:rs13029910的CC基因型频率在2-DM患者组中的含量较对照组显著升高(2.7%比0.7%,P=0.021),CC基因型个体2-DM发病风险增高,Logistic回归分析显示,其OR值(比值比)为4.266(P=0.035)。rs12329083(A/T)、rs12465425(G/T)、rs2861814(C/T)及rs11692815(A/G)位点的基因型频率、等位基因频率在2-DM组与正常对照组中的分布差异均无统计学意义(P>0.05)。结论:Cnb1基因可能与上海地区人群2-DM的遗传易感性有关,其中rs13029910多态性位点的基因型CC与2-DM发病风险增高相关。     

2型糖尿病遗传易感性与CAPN-10基因多态性的相关性研究

目的探讨2型糖尿病(T2DM)遗传易感性与CAPN-10基因多态性的关系。方法采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术对100例T2DM患者(病例组)和100例健康者(对照组)CAPN-10基因SNP19(rs3842570)、SNP43(rs3792267)和SNP63(rs5030952)多态性位点进行基因分型。结果病例组CAPN-10基因43位点的GG基因型频率和G等位基因频率显著高于对照组,差异有统计学意义(P<0.05);19位点和63位点的基因型频率、等位基因频率在病例组与对照组分布差异均无统计学意义(P>0.05)。结论 CAPN-10基因SNP43(rs3842570)位点与T2DM的发生有相关性,而SNP19(rs3842570)和SNP63(rs5030952)位点则与T2DM的发生无相关性。     

人类ErbB2转录因子1基因多态性与陕西汉族人群胃癌的关系研究

目的探讨人类ErbB2转录因子1(TOB1)基因多态性与陕西汉族人群胃癌之间的关系。方法选取320例胃癌患者为胃癌组,350例经胃镜检查及病理活检排除胃癌的门诊患者为对照组,对TOB1基因4个候选单核苷酸多态性(SNP)位点(rs61482741、rs34700818、rs12601477、rs4626)进行基因分型。分析TOB1基因候选SNP位点等位基因、基因型、显性模式和隐性模式频率与胃癌风险的关系;分析TOB1基因候选SNP位点连锁不平衡情况。结果胃癌组与对照组TOB1基因4个候选SNP位点基因分型结果均符合哈迪-温伯格平衡(P0.05)。TOB1基因易感位点包括内含子区域rs61482741位点G等位基因(P=0.011,OR=1.42,95%CI=1.15～1.78)、GG基因型(P=0.016,OR=1.91,95%CI=1.18～3.23)、显性模式GG+CG基因型(P=0.032,OR=1.44,95%CI=1.05～1.93)、隐性模式GG基因型(P=0.043,OR=1.68,95%CI=1.03～2.74);外显子区域rs4626位点G等位基因(P=0.006,OR=1.41,95%CI=1.16～1.76)、GG基因型(P=0.006,OR=1.85,95%CI=1.20～2.85)、显性模式GG+AG基因型(P=0.023,OR=1.53,95%CI=1.10～2.16)、隐性模式GG基因型(P=0.028,OR=1.56,95%CI=1.09～2.21);内含子区域rs34700818和rs12601477位点等位基因、基因型、显性模式和隐性模式频率在胃癌组与对照组间比较,差异均无统计学意义(P0.05)。结论TOB1基因内含子区域rs61482741和外显子区域rs4626位点可能是陕西汉族人群胃癌高风险易感基因位点。     

BRCA1基因单核苷酸多态性与广东汉族女性散发性乳腺癌易感相关性研究

目的探讨BRCA1基因启动子区rs799906位点和编码区rs799917位点单核苷酸多态性（single nucleotide polymorphism,SNP）与广东汉族女性散发性乳腺癌易感性的关系。方法利用Sequenom Mass Array iPLEX GOLD系统对107例散发性乳腺癌患者及93例健康对照者的BRCA1基因两个SNP位点（rs799906,rs799917）进行检测,并对检测结果进行χ2检验和非条件Logistic回归分析。结果 rs799906位点TT、TC和CC三种基因型在病例组和对照组的分布频率有差异（χ2=8.407,P=0.018）。相对TT基因型而言,TC杂合型能增加乳腺癌发生的危险性（OR=2.566;95%CI：1.101～5.983;P〈0.05）,但等位基因T和C的频率分布无显著差异（χ2=2.169,P=0.141）。rs799917位点CC、CT和TT三种基因型的频率和等位基因C和T的频率在病例组和对照组的分布均无显著性差异（χ2=3.994,P=0.136;χ2=0.903,P=0.342）。结论 BRCA1多态性位点rs799906TC杂合型与散发性乳腺癌发病风险有相关性;而rs799917位点多态性与散发性乳腺癌发病风险无相关性。     

金属蛋白酶2基因-1306C/T多态性与冠心病的关系

目的:研究金属蛋白酶2(MMP-2)基因-1306C/T多态性与冠心痛(CAD)发病的相关性.方法:采用基质辅助激光解吸电离飞行时间质谱技术(MALDI-TOF MS),检测283例冠心病患者与161例对照组人群MMP-2基因-1306C/T位点的基因型和等位基因的分布.结果:MMP-2基因-1306C/T位点基因型频率及等位基因频率在两组分布差异有统计学意义(P＜0.01),经Logistic回归分析后,CC基因型携带者患冠心病风险是T等位基因携带者(CT+TT)的2.038倍(OR=2.038,95％CI=1.193-3.481,P＜0.01).结论:MMP-2基因-1306C/T位点与冠心病发病的危险性相关,CC基因型可能是冠心病发病的遗传危险因素.     

维生素D结合蛋白基因多态性与结直肠癌的相关性研究

目的 探讨大连市汉族人群维生素D结合蛋白(VDBP)基因的2个单核苷酸多态性(SNP)位点rs4588和rs7041与结直肠癌(CRC)易感性的关系.方法 选择2015年1月至12月大连医科大学附属第一医院收治的120例汉族CRC患者作为研究对象,纳入CRC组.采用简单随机抽样法选择同期于大连市血液中心无偿献血的127例汉族健康献血者纳入对照组.采用TaqMan-MGB探针实时荧光PCR技术对受试者全血提取DNA样本的rs4588和rs7041位点进行扩增.采用x2检验统计学方法比较2组受试者VDBP基因rs4588和rs7041位点各基因型及等位基因频率分布的差异.本研究遵循的程序符合大连血液中心人体实验委员会制定的伦理学标准,得到该委员会批准.结果 ①经Hardy-Weinberg遗传平衡检验,CRC组和对照组rs7041和rs4588位点基因型分布均符合Hardy-Weinberg遗传平衡定律(CRC组:x2 =2.13、1.64,对照组:x 2=0.70、1.32;P＞0.05).②CRC组患者VDBP基因rs7041位点的TT基因型频率、GT基因型频率、GG基因型频率、T等位基因频率及G等位基因频率分别为45.0％、48.3％、6.7％、69.2％及30.8％,对照组分别为52.8％、41.7％、5.5％、73.6％及26.4％;2组rs7041位点基因型频率及等位基因频率分别比较,差异均无统计学意义(x2=1.491、1.201,P＞0.05).③CRC组患者VDBP基因rs4588位点的CC基因型频率、AC基因型频率、AA基因型频率、C等位基因频率及A等位基因频率分别为44.2％、48.3％、7.5％、68.3％及31.7％,对照组分别为44.9％、50.3％、4.7％、70.1％及29.9％;2组rs4588位点基因型频率及等位基因频率分别比较,差异亦均无统计学意义(x2=0.843、0.176,P＞0.05).结论 本研究未发现大连地区汉族人群VDBP基因rs7041和rs4588位点的SNP与CRC易感性相关.     

Polymorphisms in second intron of the FGFR2 gene are associated with the risk of early-onset breast cancer in Chinese Han women

Fibroblast growth factor receptor 2 (FGFR2) plays an important role in tumor cell growth, invasiveness, motility, and angiogenesis. Several single-nucleotide polymorphisms (SNPs) in the second intron of the FGFR2 gene are associated with the risk of breast cancer. In this study, we determined whether these SNPs of the FGFR2 gene are associated with early onset of non-familial breast cancer in a Chinese Han population. Recruited were 118 female breast cancer patients who were less than or equal to 35 years of age and without a family history of breast cancer, and 104 age-matched healthy controls. Six SNPs of the second intron of the FGFR2 gene, including rs2981428C/A (i.e., a change at this particular site from nucleotide C to A), rs11200014G/A, rs2981579C/T, rs1219648A/G, rs2420946C/T, and rs2981582C/T, were detected using matrix-assisted laser desorption/ionization mass spectrometry. The data showed that the homozygotes at each minor allele, rs11200014 (AA), rs1219648 (GG), rs2420946 (TT), and rs2981582 (TT), were significantly associated with an increased risk of early-onset non-familial breast cancer. The haplotype containing rs11200014A, rs1219648G, rs2420946T and rs2981582T also exhibited a significantly higher distribution in patients compared to controls (OR=1.784, 95% CI=1.161-2.744). In stratified analyses, each of the above four SNPs conferred a significantly greater risk of estrogen receptor-positive breast cancer, compared to estrogen receptor-negative breast cancer that is more resistant to treatment. Our data demonstrate that these four SNPs of the FGFR2 gene are associated with the risk of breast cancer at a young age in Chinese Han women.     

Genetic variation in interleukin-10 gene and risk of oral cancer

BACKGROUND: Common genetic variants in immune and inflammatory response genes can affect the risk of developing oral cancer. Interleukin-10 (IL-10) is an immunosuppressive cytokine which may facilitate development of cancer by supporting tumor escape from the immune response. Inter-individual variations in IL-10 production were genetically contributed to polymorphisms within IL-10 promoter region. We determined whether single nucleotide polymorphisms (SNPs) at positions -1082 A/G (rs1800870), -819 T/C (rs1800871) and -592 A/C (rs1800872) in the IL-10 gene promoter were involved in predisposing an individual to oral cancer. METHODS: We analyzed 3 SNPS of IL-10 gene promoter in 280 patients with oral cancer and 300 age and sex matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy. RESULTS: There were significant differences in the genotype and allele distribution of -1082 A/G (rs1800870) polymorphism of the IL-10 gene among cases and controls. The -1082 G alleles carriers were associated with a significantly increased risk of oral cancer compared with the non-carriers (OR=1.821, 95% CI, 1.329-2.496, P<0.001). Haplotype analysis revealed that the GCC haplotype (defined by SNPs at positions -1082, -819 and -592) of IL-10 gene conveys the highest risk for oral cancer compared with the ATA haplotype (OR=1.716; 95% CI, 1.230-2.395; P=0.001). CONCLUSION: IL-10 gene promoter -1082 A/G (rs1800870) polymorphism, and its haplotype are significantly associated with the risk of oral cancer. Our data suggests that IL-10 gene plays an important role in the development of oral cancer.     

Haplotype-based association of four lymphotoxin-alpha gene polymorphisms with the risk of coronary artery disease in Han Chinese

Lymphotoxin-alpha (LTA), a pro-inflammatory cytokine, has been implicated in the pathogenesis of coronary atherosclerosis. Meanwhile, association of some single nucleotide polymorphisms (SNPs) of LTA gene with coronary artery disease (CAD) has been evaluated; however, the results are irreproducible. We therefore investigated the relationship between four SNPs of LTA gene and CAD in Han Chinese: G+10A (rs1800683, 5'-untranslated region), A+80C (rs2239704, 5'-untranslated region), T+496C (Cys13Arg, rs2229094, exon 2), and C+804A (Thr26Asn, rs1041981, exon 3). Genotyping was performed in 438 CAD patients and 330 healthy controls. Single-locus analysis showed that the genotype and allele frequencies of G+10A polymorphism exhibited marginal differences between CAD patients and controls, although no statistical significance was observed after the Bonferroni correction. Logistic regression analysis revealed that GG genotype of G+10A polymorphism was significantly associated with the risk of CAD under the dominant mode, whereas no significant association was detected between A+80C polymorphism and CAD. In contrast, individuals carrying TT or TC genotype of T+496C polymorphism showed a decreased CAD risk relative to those with CC genotype under the recessive mode. Likewise, CC genotype of C+804A polymorphism was associated with a protective effect on CAD under the dominant mode. Further, in haplotype analysis, the haplotype G-C-T-C (in order of rs1800683, rs2239704, rs2229094 and rs1041981) was significantly associated with a decreased risk of CAD after assigning the most common haplotype A-C-T-A as a reference. In conclusion, we show a protective effect of the haplotype G-C-T-C on the occurrence of CAD, suggesting the involvement of LTA in CAD pathogenesis.     

中国汉族人脂联素基因rs2241766及rs1501299多态性与2型糖尿病及代谢指标的关系

目的在中国汉族人群中,观察脂联素基因rs2241766(T>G)和rs1501299(G>T)多态性与2型糖尿病及胰岛素抵抗的关系。方法使用聚合酶链反应-单链构象多态性(PCR-SSCP)银染技术结合基因直接测序法,对糖耐量正常(NGT)者150例及2型糖尿病(T2DM)患者285例,进行基因的检测及代谢指标的观察。结果 rs2241766 TT、TG、GG基因型和rs1501299 GG、GT、TT基因型,在T2DM组及NGT组中的分布存在显著差异。rs2241766 G(TG+GG)等位基因携带者患T2DM的风险增加2倍,而rs1501299 TT携带者患T2DM的风险下降;偏相关分析显示,rs2241766 G(TG+GG)等位基因与HOMAIR呈现正相关,rs1501299 TT基因型与HOMAIR呈现负相关;rs2241766 G携带者以及rs1501299 TT携带者的体质量指数(BMI)、腰臀部(WHR)、体脂百分比(%body fat)显著升高。结论 rs2241766 G是中国汉族人T2DM的危险因素,而rs1501299 TT则是保护因素。     

葡萄糖激酶基因3个标签单核苷酸多态性位点与2型糖尿病的相关性研究

目的探讨葡萄糖激酶(GCK)基因3个标签单核苷酸多态性(tagSNPs)位点rs2971672、rs2268573、rs2300587与2型糖尿病的关系。方法选取2013年8月至2014年12月在中山大学附属中山医院住院的中国南方汉族2型糖尿病患者499例(2型糖尿病组),同时选择同期在该院康体保健中心体检的汉族健康人499例作为对照组,对GCK基因的3个tagSNPs位点采用改良多重高温连接酶检测反应技术(iMLDR)进行基因分型,应用Hardy-Weinberg平衡规律检测标本代表性,采用χ~2检验、Logistic回归分析比较2型糖尿病组和对照组基因型和等位基因频率的差异,并在加性、显性和隐性3种遗传模型下对各SNP位点进行相关性分析。应用Haploview软件构建GCK基因3个tagSNPs位点的单体型,分析是否存在连锁不平衡(LD)及不同的GCK单体型与2型糖尿病易感性的关系。结果 rs2268573、rs2300587的基因型(χ~2=3.361、2.076,均P0.05)和等位基因频率(χ~2=0.222、1.980,均P0.05)在2型糖尿病组和对照组之间差异均无统计学意义。rs2971672的基因型(χ~2=6.896,P0.01)和等位基因分布(χ~2=4.708,P0.05)在2型糖尿病组和对照组之间差异有统计学意义。在显性遗传模式下以及在加性遗传模式下,rs2971672的基因型分布在2型糖尿病组和对照组之间的差异有统计学意义(显性遗传模式下OR=1.74,95%CI:1.17~2.57,P0.01;加性遗传模式下OR=1.51,95%CI:1.06~2.14,P0.05)。GCK基因3个位点中的rs2971672和rs2300587有一个LD域,其中TC、TA、CA3种主要单体型,单体型TA和CA均降低个体患2型糖尿病的风险,OR值分别为0.81(95%CI:0.66~1.00,P0.05)和0.78(95%CI:0.62~0.98,P0.05)。结论在汉族人群中,GCK基因区域的rs2971672位点与糖尿病遗传易感性密切相关,而rs2268573、rs2300587位点与糖尿病遗传易感性无明确相关性。rs2971672和rs2300587的LD域单体型TA和CA均降低个体患2型糖尿病的风险。     

CYP4F2基因单核苷酸多态与缺血性脑卒中的相关性

目的 探讨CYP4F2 基因多态与中国北方汉族人群缺血性脑卒中的相关性.方法 采用病例-对照研究,检测CYF4F2基因rs2108622、rs3093100、rs3093105、rs3093135、rs1558139位点,以及该基因rs2108622-rs3093100-rs3093105-rs3093135构成的单倍型在对照组、IS组及不同性别组中的多态分布.结果 CYP4F2基因rs2108622位点GG基因型可能是男性缺血性脑卒中患者的独立的风险因素(P=0.018,OR=2.53,95%CI 1.15～5.56),且其风险性主要来源于G等位基因(P=0.013,OR=1.48,95%CI 1.09～2.02).rs2108622-rs3093100-rs3093105-rs3093135构成的GGGT单倍型与男性缺血性脑卒中具有相关性,GGGT单倍型可能是IS的危险单倍型(OR=1.545,95%CI 1.144～2.087,P=0.004).结论 CYP4F2基因的多态与男性IS具有相关性,可显著增加男性IS的患病风险.     

The association of CYP2C9 gene polymorphisms with colorectal carcinoma in Han Chinese

BACKGROUND: Cytochrome P450 (CYP) 2C9 is an important enzyme involved in xenobiotics metabolism. This study investigated the association of CYP2C9 gene coding region polymorphisms with colorectal cancer (CRC) in Chinese Han population. METHODS: Four hundred and eighty-three healthy controls and 286 sporadic CRC patients participated in this study. Direct sequencing was used to identify the sequence polymorphisms. RESULTS: We detected the significant association of 2 coding region SNPs, rs1057910 and rs1057911, of CYP2C9 with the risk of developing sporadic CRC for Han Chinese. These 2 SNPs showed a strong linkage disequilibrium (LD) (r(2)=0.97, D'=0.985). Significantly different minor allele frequencies were found for SNPs rs1057910 and rs1057911 between the cases (7% and 7.2%, respectively) and controls (3% and 2.9%, respectively) with adjusted P=0.0004 and 0.0002, respectively. Individuals heterozygous for rs1057910A/C or rs1057911A/T showed 2.589-fold (95% CI: 1.549-4.330) or 2.770-fold (95% CI 1.653-4.643) increased risk of developing sporadic CRC. We did not detect any homozygote minor allele carrier for either rs1057910 or rs1057911 in our study population. The CRC association appeared to be more evident for individuals over age 50 y, for men, and for rectum cancer site. CONCLUSION: There is an association of CYP2C9 coding region polymorphisms with the risk of developing CRC in Han Chinese after genotyping cases and controls recruited from different locations in China.     

自噬相关基因5基因多态性及其单倍体型与帕金森病的相关性研究

目的 探讨自噬相关基因5( Atg5)基因3个标签单核苷酸多态性(Tag SNP,rs17587319C/G、rs573775C/T、rs9486315C/T)及其单倍体型与帕金森病(PD)发病的关系.方法 采用病例-对照研究,PD患者80例(病例组)和健康体检者87例(对照组)为对象,应用聚合酶链反应-限制性酶切片段长度多态性分析方法(PCR-RFLP)检测Atg5 Tag SNP rs17587319C/G、rs573775C/T、rs9486315C/T,并分析其基因型及等位基因频率在正常人群及PD患者中的分布特点.结果 Atg5 Tag SNP rs17587319C/G的C等位基因频率病例组为89.4％ (143/160),对照组为74.7％(130/174),差异有统计学意义(P＜0.01);病例组CC基因型频率为78.7％ (63/80),对照组为58.6％(51/87),差异有统计学意义(P＜0.01).SNP rs573775C/T和rs9486315C/T的等位基因频率及基因型频率在两组问的差异无统计学意义(P＞0.05).Logistic回归分析结果SNP rs17587319C/G的CC基因型与PD的发病有独立相关性(P＜0.01).单倍体型分析结果病例组中H1、H2单倍体型的频率高于对照组(P＜0.05和＜0.01).结论 H1,H2单倍体型和Atg5 Tag SNP rs17587319C/G的C等位基因可能是PD的危险因素.     

The T-1237C polymorphism of the Toll-like receptor-9 gene is associated with chronic kidney disease in a Han Chinese population

Chronic kidney disease (CKD) is increasingly recognized as a global public health problem. As inflammatory processes and genetic factors are involved in the pathogenesis of CKD, we have investigated the potential genetic contribution of Toll-like receptor (TLR) gene polymorphisms in CKD. In a case-control association study, 149 CKD patients and 429 healthy controls were genotyped by real-time polymerase chain reaction. CKD patients were defined as kidney damage (albuminuria, proteinuria or hematuria) or glomerular filtration rate < 60 ml/min/1.73 m(2) for 3 months or more. Single nucleotide polymorphisms (SNPs) at TLR-2 G2408A, TLR-4 A12874G and C13174T, and TLR-9 T-1237C, T-1486C, and G1635A were assessed, and linkage disequilibrium calculations and haplotype association analysis were undertaken. The functions of TLR-9 have been documented to recognize the viral and bacterial CpG DNA sequences, whereas detects microbe-derived peptidoglycan and lipopeptides and TLR-4 binds lipopolysaccharides. SNPs within the TLR genes may influence promoter activity, mRNA conformation and subcellular localization, and/or protein structure and function. Our results show that only the TLR-9 T-1237C and G1635A gene polymorphisms demonstrate an association with CKD (p = 0.002 and p = 0.04, respectively). The TLR-9 TCA haplotype at T-1237C, T-1486C, and G1635A was associated with a lower risk of CKD, whereas the TTA haplotype was associated with a higher risk of CKD. In the Han Chinese population, those who carry the C and A alleles at SNPs T-1237C and G1635A in the TLR-9 gene appear to be more susceptible to the development of CKD.