TGF-β1基因多态性与广东地区子痫前期相关性研究

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目的:探讨转化生长因子β1(TGF-β1)基因4个位点-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SNa Pshot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-β1 4个SNP基因型分布及等位基因频率的差异,并对+869T/C、-509C/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%vs51.14%,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%vs42.33%,P=0.021,OR=0.618,95%CI为0.398~0.961)。结论:(1)TGF-β1基因+869T/C、-509C/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-800G/A、+915G/C多态性。(2)TGF-β1基因SNP+869T/CCC基因型、C等位基因,-509C/TT等位基因可能是广东汉族妇女PE的危险因素,而+869T/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 investigate the single nucleotide polymorphisms (SNP) of the four sites of TGF-β1 -800G / A, -509C / T, + 869T / C and +915G / C Haplotype and preeclampsia (PE). Methods: A total of 176 Han pregnant women were enrolled from Guangdong Province, the third affiliated hospital of Guangzhou Medical University from January to December 2015, including 88 PE patients (PE group) and 88 normal pregnant women (control group). Using SNa Pshot technology to detect the genotypes of TGF-β1 at 4 loci, we analyzed the distribution of genotypes and allele frequencies of TGF-β1 in PE and control groups, and analyzed the differences of + 869T / C, -509C / T two sites to construct haplotype analysis. Results: (1) TGF-β1 + 869T / C and -509C / T polymorphisms were present in Han women in Guangdong, China. However, no polymorphisms of -800G / A and +915G / C were found at present. (2) The frequencies of CC genotype and C allele in PE group at 869T / C locus were significantly higher than those in control group (44.32% vs 27.27%, P = 0.028, OR = 1.935, 95% CI 1.028-3.639, 68.18% vs 56.25%, P = 0.014, OR = 1.667, 95% CI: 1.079-2.575). The TT genotype and T allele were significantly decreased (5.68% vs 14.77%, P = 0.040, OR = 0.348, 95% CI (0.118 ~ 1.021; 31.82% vs 43.75%, P = 0.014, OR = 0.600, 95% CI 0.388-0.927). There was no significant difference in CT genotype between the two groups (52.27% vs 57.95%, P = 0.272). (3) Compared with the control group, there was no significant difference in the distribution of CC, CT and TT genotypes between PE and control group (14.77% vs 23.86%, P = 0.090; 47.73% vs 50.00%, P = 0.440; 37.50% vs 26.4%, P = 0.072), while the C allele was significantly decreased (38.64% vs 48.86%, P = 0.034, OR = 0.659, 95% CI 0.431-1.006) .14%, P = 0.034, OR = 1.518, 95% CI 0.994 ~ 2.318). (4) The haplotype analysis showed that the CT haplotypes constructed by + 869T / C and -509C / T were significantly increased in PE group (62.79% vs 49.43%, P = 0.008, OR = 1.727,95 % CI was 1.125-2.651), while the TC haplotype was significantly decreased (31.40% vs42.33%, P = 0.021, OR = 0.618, 95% CI 0.398-0.961). Conclusion: (1) The + 869T / C and -509C / T SNPs of TGF-β1 gene may be related to the occurrence of PE in Han women of Guangdong province in Guangdong Province, while the -800G / A and +915G / C polymorphisms are not yet found. (2) The SNP + 869T / CCC genotype, C allele and -509C / TT allele of TGF-β1 gene may be the risk factors for PE in Guangdong Han women. However, the + 869T / CTT genotype, T allele, The -509C / TC allele may be a protective factor. (3) The C-T haplotype composed of two polymorphic loci may be the risk factor for PE in Han women in Guangdong, China, while the T-C haplotype is the protective factor.
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