TCF7L2基因（rs7903146、rs290487、rs11196205、rs12255372）多态性与妊娠期糖尿病

发布时间：2018-10-13 08:48

【摘要】：目的：本研究对转录因子7类似物2(transcription factor7-like2，TCF7L2)基因的（rs7903146C/T、rs290487C/T、rs11196205G/C、rs12255372G/T）单核苷酸多态性进行分析，比较妊娠期糖尿病（gestational diabetes mellitus，GDM）和正常妊娠组两种基因型分布频率，探讨TCFTL2基因与江西籍汉族人群妊娠期糖尿病遗传易感性的相关关系。方法：实验对象：2010年01月～2013年07月在江西省妇幼保健院住院治疗和分娩的江西籍汉族孕妇，GDM孕妇100例及同期入院的正常健康孕妇100例。方法：采用病例对照研究方法，记录研究对象的一般临床指标包括：年龄，孕周，分娩前的身体质量指数（body mass index BMI），新生儿出生体重及孕妇糖代谢的相关指标。用血液基因组DNA提取试剂盒（离心柱型）提取所有受试者基因组DNA，用等位基因特异PCR（allele-specific polymerase chain reactionAS-PCR）技术检测GDM孕妇与正常孕妇TCF7L2基因rs7903146、rs290487、rs11196205、rs12255372位点基因型，，计算检验人群各位点基因型和等位基因频率，并用统计学方法分析TCF7L2基因这四个位点基因型和等位基因与GDM发病相关关系。结果： 1、在所有受试者中，TCF7L2基因rs7903146C/T位点CC、CT及TT三种基因型分布频率分别为47.5%、37.0%及15.5%; rs290487C/T位点CC、CT及TT三种基因型分布频率分别为14.0%、35.0%及51.0%; rs11196205G/C位点GG、CC基因型分布频率为99.5%、0.5%，未发现GC基因型者;rs12255372G/T位点GG基因型分布频率为100%,未发现GT及TT基因型者。 2、TCF7L2基因rs7903146、rs290487、rs11196205、rs12255372位点基因型分布均符合Hardy-Weinberg平衡定律(P＞0.05)，TCF7L2基因rs7903146两组的基因型和等位基因分布均有统计学差异（P0.05),病例组中TT基因型频率明显高于对照组。TT基因型GDM发病风险与CT+CC基因型相比，比数比(oddsratio OR)为4.195(95％CI1.715～10.266);P=0.002。rs290487C/T、rs11196205G/C、rs12255372G/T位点各基因型分布及等位基因频率在病例组和对照组间无差别。 3、两组一般临床资料及糖代谢相关生化指标比较得出孕妇分娩时BMI、空腹血糖（fasting blood-glucose FPG）、胰岛素（fasting insulin FINS）、胰岛素抵抗指数（HOMA Insulin resistance index HOMA-IR）病例组是明显高于对照组，差异均有统计学意义（P＜0.05）。 4、经logistic回归校正相关混杂因素后显示，rs7903146的TT基因型发生GDM风险是C等位基因携带者的2.77倍。并BMI、FPG、FINS与GDM发病有一定的相关性。结论： TCF7L2基因rs7903146的多态性可能与江西籍汉族人群GDM发病相关,TT基因型可能是GDM发生的危险因素,同时BMI、FPG、FINS均与GDM的发病有一定的相关性。
[Abstract]:Objective: to analyze the single nucleotide polymorphisms (rs7903146C/T,rs290487C/T,rs11196205G/C,rs12255372G/T) of transcription factor 7 analogue 2 (transcription factor7-like2,TCF7L2) gene and compare the genotypes distribution between (gestational diabetes mellitus,GDM and normal pregnant women. To investigate the relationship between TCFTL2 gene and genetic susceptibility to gestational diabetes mellitus (GDM) in Jiangxi Han nationality population. Methods: from January 2010 to July 2013, 100 pregnant women of Jiangxi Han nationality, 100 pregnant women with GDM and 100 normal pregnant women who were hospitalized in Jiangxi Maternal and Child Health Care Hospital were enrolled in the study. Methods: a case-control study was conducted to record the general clinical parameters of the subjects, including age, gestational age, body mass index (body mass index BMI),) before delivery, birth weight of newborns and glucose metabolism of pregnant women. The genomic DNA, of all subjects was extracted by the blood genomic DNA extraction kit (centrifuge column type). The allele-specific PCR (allele-specific polymerase chain reactionAS-PCR) technique was used to detect the rs7903146,rs290487,rs11196205,rs12255372 loci of TCF7L2 gene in GDM pregnant women and normal pregnant women. The frequencies of genotypes and alleles of TCF7L2 gene were calculated and analyzed. The relationship between the four loci genotype and allele of TCF7L2 gene and the pathogenesis of GDM was analyzed by statistical method. Results: 1. In all subjects, the distribution frequencies of CC,CT and TT genotypes of rs7903146C/T locus and TT locus of TCF7L2 gene were 47.5% and 15.5%, CC,CT and TT genotype frequencies of rs290487C/T locus were 14.00.35% and 51.0%, respectively, and GG,CC genotype distribution of rs11196205G/C locus was 14.0% and 51.0%, respectively. The distribution frequency of GG genotype at rs12255372G/T locus was 100kum, and that of GT and TT genotype was not found. 2the rs7903146,rs290487,rs11196205,rs12255372 genotype distribution of TCF7L2 gene obeys the equilibrium rule of Hardy-Weinberg (P > 0. 05), and the rs7903146,rs290487,rs11196205,rs12255372 genotype distribution of TCF7L2 gene rs7903146 gene is in accordance with the law of Hardy-Weinberg balance (P > 0. 05). The frequency of TT genotype in the case group was significantly higher than that in the control group. The risk of TT genotype GDM was higher than that of CT CC genotype. The ratio of (oddsratio OR) to (oddsratio OR) was 4.195 (95%CI1.715~10.266), and the genotype distribution and allelic frequency of P0. 002.rs290487C / Tnrs11196205G / Cnrs12255372G / T locus were not different between the case group and the control group. 3. The general clinical data and the biochemical indexes related to glucose metabolism were compared between the two groups. BMI, fasting blood glucose (fasting blood-glucose FPG), insulin (fasting insulin FINS), insulin resistance index (HOMA Insulin resistance index HOMA-IR) was significantly higher in the case group than in the control group. The difference was statistically significant (P < 0. 05). 4. The TT genotype of rs7903146 was 2.77 times more likely to develop GDM than that of C allele carriers after logistic regression adjusted the associated confounding factors. There was a certain correlation between BMI,FPG,FINS and GDM. Conclusion: the polymorphism of TCF7L2 gene rs7903146 may be associated with the incidence of GDM in Jiangxi Han population, and the TT genotype may be a risk factor for GDM, and BMI,FPG,FINS may be associated with the pathogenesis of GDM.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R714.256

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