TGF-β1基因多态性与广东地区子痫前期相关性研究

Studies of the association between polymorphisms of TGF-β1 gene and the susceptibility of preeclampsia in Guangdong area

目的：探讨转化生长因子β1（ TGF-β1）基因4个位点-800 G/A、-509 C/T、＋869 T/C、＋915 G/C的单核苷酸多态性（ SNP ）及其构成的单体型与子痫前期（ PE ）的相关性。方法：随机选取2015年1月至12月于广州医科大学附属第三医院住院的广东地区汉族孕妇176例,其中PE患者88例（ PE组）、正常妊娠88例（对照组）。利用SNaPshot技术对TGF-β1基因4个位点进行基因分型检测,分析PE 组与对照组的TGF-β14个SNP基因型分布及等位基因频率的差异,并对＋869 T/C、-509 C/T两个位点构建单体型分析。结果：（1）中国广东地区汉族妇女中存在TGF-β1＋869T/C、-509C/T多态性,暂未发现-800G/A、＋915G/C多态性。（2）PE组＋869T/C位点CC基因型、C等位基因频率明显高于对照组（44.32% vs 27.27%, P=0.028, OR=1.935,95%CI 为1.028~3.639；68.18% vs 56.25%,P=0.014,OR=1.667,95%CI为1.079~2.575）,TT基因型和T等位基因则明显下降（5.68% vs 14.77%,P=0.040,OR=0.348,95%CI为0.118~1.021；31.82% vs 43.75%,P=0.014,OR=0.600,95%CI为0.388~0.927）；两组CT基因型分布无明显差异（52.27% vs 57.95%,P=0.272）。（3） PE 与对照组比较,-509C/T位点CC、CT、TT基因型分布无明显差异（14.77% vs 23.86%,P=0.090；47.73% vs 50.00%, P=0.440；37.50% vs 26.14%,P=0.072）,而C等位基因明显下降（38.64% vs 48.86%, P=0.034, OR=0.659,95%CI 为0.431~1.006）, T 等位基因明显升高（61.36% vs 51.14%,P=0.034,OR=1.518,95%CI 为0.994~2.318）。（4）单体型分析发现,由＋869T/C、-509C/T两个位点构建的C-T单体型在PE组明显增加（62.79% vs 49.43%,P=0.008, OR=1.727,95%CI 为1.125~2.651）,而 T-C 单体型明显下降（31.40% vs 42.33%,P=0.021,OR=0.618,95%CI 为0.398~0.961）。结论：（1） TGF-β1基因＋869 T/C、-509 C/T SNPs可能与中国广东地区汉族妇女PE发生有关,而暂未发现-800 G/A、＋915 G/C多态性。（2） TGF-β1基因SNP＋869 T/CCC 基因型、C 等位基因,-509 C/TT等位基因可能是广东汉族妇女 PE 的危险因素,而＋869 T/CTT 基因型、T 等位基因,-509C/TC等位基因可能是保护因素。（3）2个多态位点构成的C-T单体型可能是中国广东地区汉族妇女PE的危险因素,T-C单体型则是保护因素。

Objective：To study the relationship of the SNP and Haplotype of four gene loci of TGF-β1 genes including -800G/A、-509C/T、＋869T/C、＋915G/C and preeclampsia, and research the pathogenesis of preeclampsia. Methods：Randomly selected 176 pregnant Han women in Guangdong province attending at the Third Affiliated Hospital of Guangzhou Medical College hospital from Jan. 1 to Dec. 31 2015,including research group （88 women with pre-eclampsia） and control group （88 normal pregnant women） . Detect the SNP of TGF-β1 and its genes -800G/A、-509C/T、＋869T/C、＋915G/C by SNaPshot. Results：（1） The SNPs of ＋869T/C and -509C/T existed in pregnant Han women in Guangdong province. The SNPs of -800G/A and＋915G/C had not been detected. （2）The CC genotype and C allele frequencies of＋869T/C in research group were significantly increased than that in control group respectively, but TT genotype and T allele were significantly lower（P〈0. 05）. No difference between the two groups of CT genotype distribution （P〉0. 05）. （3）To compare with the control group,the CC, CT,TT genotype distribution of-509C/T had no obvious difference （P〉0. 05）,but the C allele were significantly decreased and the T allele frequencies were markedly increased （ P〈0 . 05 ） . （ 4 ） The haplotype analysis of ＋869 T/C and -509 C/T showed that the haplotype frequencies of C-T were significantly higher in research group than in control group,but the haplotype frequen-cies of T-C were significantly decreased （ P〈0 . 05 ） . Conclusion：Han Pregnant in Guangdong province were be found：（1） The SNPs of ＋869T/C and -509C/T may be associated with the susceptibility of PE. And temporarily not found the -800G/A and ＋915G/C loci polymor-phism. （2）The CC genotype and C allele of ＋869T/C,the T allele of 509C/T may be a risk factor for PE. And the TT genotype,T allele of＋869T/C,C allele of-509C/T may be a protec-tive factor. （3）The haplotype C-T may be a risk factors and the haplotype of T-C is a protective factor.