發(fā)布時間：2018-10-13 08:48

【摘要】：目的： 本研究對轉(zhuǎn)錄因子7類似物2(transcription factor7-like2，TCF7L2)基因的（rs7903146C/T、rs290487C/T、rs11196205G/C、rs12255372G/T）單核苷酸多態(tài)性進行分析，比較妊娠期糖尿病（gestational diabetes mellitus，GDM）和正常妊娠組兩種基因型分布頻率，探討TCFTL2基因與江西籍漢族人群妊娠期糖尿病遺傳易感性的相關(guān)關(guān)系。 方法： 實驗對象：2010年01月～2013年07月在江西省婦幼保健院住院治療和分娩的江西籍漢族孕婦，GDM孕婦100例及同期入院的正常健康孕婦100例。 方法：采用病例對照研究方法，記錄研究對象的一般臨床指標包括：年齡，孕周，分娩前的身體質(zhì)量指數(shù)（body mass index BMI），新生兒出生體重及孕婦糖代謝的相關(guān)指標。用血液基因組DNA提取試劑盒（離心柱型）提取所有受試者基因組DNA，用等位基因特異PCR（allele-specific polymerase chain reactionAS-PCR）技術(shù)檢測GDM孕婦與正常孕婦TCF7L2基因rs7903146、rs290487、rs11196205、rs12255372位點基因型，，計算檢驗人群各位點基因型和等位基因頻率，并用統(tǒng)計學(xué)方法分析TCF7L2基因這四個位點基因型和等位基因與GDM發(fā)病相關(guān)關(guān)系。 結(jié)果： 1、在所有受試者中，TCF7L2基因rs7903146C/T位點CC、CT及TT三種基因型分布頻率分別為47.5%、37.0%及15.5%; rs290487C/T位點CC、CT及TT三種基因型分布頻率分別為14.0%、35.0%及51.0%; rs11196205G/C位點GG、CC基因型分布頻率為99.5%、0.5%，未發(fā)現(xiàn)GC基因型者;rs12255372G/T位點GG基因型分布頻率為100%,未發(fā)現(xiàn)GT及TT基因型者。 2、TCF7L2基因rs7903146、rs290487、rs11196205、rs12255372位點基因型分布均符合Hardy-Weinberg平衡定律(P＞0.05)，TCF7L2基因rs7903146兩組的基因型和等位基因分布均有統(tǒng)計學(xué)差異（P0.05),病例組中TT基因型頻率明顯高于對照組。TT基因型GDM發(fā)病風(fēng)險與CT+CC基因型相比，比數(shù)比(oddsratio OR)為4.195(95％CI1.715～10.266);P=0.002。rs290487C/T、rs11196205G/C、rs12255372G/T位點各基因型分布及等位基因頻率在病例組和對照組間無差別。 3、兩組一般臨床資料及糖代謝相關(guān)生化指標比較得出孕婦分娩時BMI、空腹血糖（fasting blood-glucose FPG）、胰島素（fasting insulin FINS）、胰島素抵抗指數(shù)（HOMA Insulin resistance index HOMA-IR）病例組是明顯高于對照組，差異均有統(tǒng)計學(xué)意義（P＜0.05）。 4、經(jīng)logistic回歸校正相關(guān)混雜因素后顯示，rs7903146的TT基因型發(fā)生GDM風(fēng)險是C等位基因攜帶者的2.77倍。并BMI、FPG、FINS與GDM發(fā)病有一定的相關(guān)性。 結(jié)論： TCF7L2基因rs7903146的多態(tài)性可能與江西籍漢族人群GDM發(fā)病相關(guān),TT基因型可能是GDM發(fā)生的危險因素,同時BMI、FPG、FINS均與GDM的發(fā)病有一定的相關(guān)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.
【學(xué)位授予單位】：南昌大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R714.256

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