转化生长因子β1基因多态性与广东地区汉族妊娠期糖尿病的相关性研究

The Correlation between the Polymorphisms of TGF-β1 Gene and the Pathogenesis of Gestational Diabetes Mellitus in Guangdong Chinese Han Women

目的:探讨转化生长因子β1(TGF-β1)4个基因位点:-800G/A、-509C/T、+869T/C、+915G/C的单核苷酸多态性(SNP)及其构成的单体型与中国广东地区汉族女性妊娠期糖尿病(GDM)发生风险的相关性。方法:回顾性分析2014年9月至2017年3月在广州医科大学附属第三医院产科产前检查并分娩的广东地区汉族女性240例(正常对照组120例,GDM组120例)。利用SNaPshot基因测序技术对各组TGF-β1的4个基因位点(-800G/A、-509C/T、+869T/C、+915G/C)进行基因分型检测,并对各个位点的基因型频率、等位基因频率及其构成的单体型与GDM的相关性进行比较分析。结果:①GDM组与正常对照组TGF-β1的+915 G/C、-800G/A 2个基因位点暂未发现SNP多态性,而-509C/T、+869T/C 2个基因位点存在多态性。②GDM组+869T/C位点的CC基因型、C等位基因频率明显高于正常对照组(55.83%vs 32.50%、75.42%vs 54.58%),而TT基因型和T等位基因明显低于正常对照组(5.00%vs 23.33%、24.58%vs 45.42%),差异均有统计学意义(P<0.05);进一步统计分析提示,CC基因型(OR 2.626,95CI 1.553~4.439)、C等位基因(OR 2.553,95%CI 1.731~3.764)可能是GDM的危险因素,TT基因型(OR 0.173,95%CI 0.069~0.435)、T等位基因(OR 0.392,95%CI 0.266~0.578)可能是GDM的保护因素。③GDM组与正常对照组-509C/T位点的CC、TT、CT基因型频率及C、T等位基因频率比较,差异均无统计学意义(P>0.05)。④单体型分析发现,与正常对照组比较,+869T/C、-509C/T 2个位点构建的C-T单体型在GDM组明显增加(65.83%vs 49.58%),而T-C和T-T单体型明显下降(19.58%vs 31.25%、5.00%vs 14.17%),差异均有统计学意义(P<0.05);进一步统计分析提示,C-T单体型可能是中国广东地区汉族女性GDM发生的危险因素(OR 1.959,95%CI 1.356~2.830),T-C单体型(OR 0.536,95%CI 0.352~0.815)、T-T单体型(OR 0.319,95%CI 0.161~0.632)可能是其保护因素。结论:GDM发病是多个基因共同作用的结果,TGF-β1+869T/C SNP位点和+869T/C、-509C/T两个SNP位点构成的C-T单体型、T-C单体型、T-T单体型可能和中国广东地区汉族女性GDM的遗传易感性有关。

Objective:To research the correlation between the SNP of four gene loci of TGF-β1 genes+869T/C,-509C/T,+915 G/C,-800G/A and haplotypes in the pathogenesis of GDM in Guangdong Chinese Han women.Methods:Randomly selected 240 cases of Han Chinese pregnant women in the Third Affiliated Hos-pital of Guangzhou Medical University from September 2014 to March 2017.120 cases assigned into normal group and the left 120 cases into GDM group.SNaPshot technique was used to detect the TGF-β1 four gene loci:+869T/C,-509C/T,+915G/C,-800G/A.Statistically analyzing the genotype frequencies and allele frequen-cies of each locus and their haplotypes to investigate the relationship between the polymorphisms of TGF-β1 gene and the risk of GDM in Guangdong Han Chinese women.Results:The SNPs of+869T/C and-509C/T existed in pregnant Han women in Guangdong province.The SNPs of-800G/A and+915G/C have not been detected.The CC genotype and C allele frequencies of+869T/C in research group were significantly increased than that in con-trol group respectively(55.83%vs 32.50%、75.42%vs 54.58%),but TT genotype and T allele were significantly lower(5.00%vs 23.33%、24.58%vs 45.42%),the two groups has significant difference(P<0.05).No differ-ence between the two groups of CT genotype distribution(44.17%vs 39.17%,P>0.05).The CC genotype(OR 2.626,95CI 1.553-4.439),C allele(OR 2.553,95%CI 1.731-3.764)may be a risk factor for GDM.The TT(OR 0.173,95%CI 0.069-0.435)genotype and T allele(OR 0.392,95%CI 0.266-0.578)may be protective factors for GDM.There was no significant difference in the distribution of CC,TT and CT genotypes in the-509C/T locus between the GDM group and the normal control group(8.33%vs11.67%、50.00%vs 39.17%、41.67%vs 49.17%,P>0.05);There was no significant difference in C and T allele frequencies between the two groups(29.17%vs 36.25%、70.83%vs 63.75%,P>0.05).The haplotype analysis showing that the C-T haplotype con-structed by the two sites of+869T/C and-509C/T was significantly increased in the GDM group compared with the normal control group(65.83%vs 49.58%),the T-C and T-T haplotypes decreased significantly(19.58%vs 31.25%、5.00%vs 14.17%),the two groups has significant difference(P<0.05).No difference between the two groups of C-C T haplotype distribution(5.00%vs 9.58%,P>0.05).The C-T haplotype may be a risk factor for GDM(OR=1.959,95%CI 1.356-2.830).The T-C haplotype(OR=0.536,95%CI 0.352-0.815)、T-T haplotype(OR=0.319,95%CI 0.161-0.632)may be protective factors for GDM.Conclusions:TGF-β1+869T/C and-509C/T SNP loci gene polymorphism were detected.TGF-β1-800G/A and+915 G/C SNP loci gene polymor-phism were not found.The TGF-β1+869T/C SNP locus may be related to the genetic susceptibility of GDM in Han women in Guangdong,China.The TGF-β1-509C/T SNP locus may not be related to the genetic susceptibility of GDM in Han women in Guangdong.The pathogenesis of GDM is the result of the interaction of multiple genes.The TGF-β1+869T/C SNP locus and the CT haplotype,TC haplotype and TT single composed of the two SNP loci of+869T/C and-509C/T.The body shape may be related to the genetic susceptibility of GDM in Han women in Guangdong,China.