TCF7L2基因多态性与妊娠期糖尿病遗传易感性的相关性

Correlation between TCF7L2 gene polymorphism and genetic susceptibility in women with gestational diabetes mellitus

目的 探讨转录因子7类似物2（TCF7L2）基因rs7903146、rs290487、rs11196205、rs12255372位点单核苷酸多态性（SNP）与妊娠期糖尿病（GDM）孕妇遗传易感性的相关性.方法 选取2010年1月-2013年7月在江西省妇幼保健院就诊的GDM孕妇100例为GDM组,选取同期入院的健康孕妇100例为对照组.孕妇入院后当日计算体质指数（BMI）,检测空腹胰岛素（FINS）及空腹血糖（FPG）水平,并计算稳态模型胰岛素抵抗指数（HOMA-IR）;采用等位基因特异PCR（AS-PCR）技术分析TCF7L2基因rs7903146、rs290487、rs11196205、rs12255372位点的基因型,并进行相关性分析.结果 （1） GDM组孕妇BMI（27.4± 3.0） kg/m2、FPG（5.6±1.0） mmol/L、FINS（6.2±3.4）mU/L、HOMA-IR1.8±1.0;对照组孕妇BMI为（24.2±2.9） kg/m2、FPG（5.3 ±0.8） mmol/L、FINS（4.5±2.8） mU/L、HOMA-IR1.2±0.8;两组分别比较,差异均有统计学意义（P＜0.05）.（2）rs7903146位点的SNP分型为CC、CT和TT共3种基因型;rs290487位点的SNP分型为CC、CT和TT共3种基因型;rs11196205位点的SNP分型为GG、CC共两种基因型;rs12255372位点的SNP分型仅为GG基因型.（3）rs7903146位点在GDM组及对照组中均以CC基因型为主,GDM组CC型频率为40％（40/100）,CT型频率为36％（36/100）,TT型频率为24％（24/100）;C等位基因频率为58％ （116/200）,T等位基因频率为42％（84/200）.对照组CC型频率为55％（55/100）,CT型频率为38％（38/100）,TT型频率为7％ （7/100）;C等位基因频率为74％（148/200）,T位基因频率为26％ （52/200）.两组分布比较,差异均有统计学意义（P＜0.05）.（4）rs290487位点在GDM组及对照组中均以TT基因型为主,GDM组CC型频率为12％（12/100）,CT型频率为36％ （36/100）,TT型频率为52％ （52/100）;C等位基因频率为30％ （60/200）,T等位基因频率为70％ （140/200）.对照组CC型频率为16％（16/100）,CT型频率为34％（34/100）,TT型频率为50％（50/100）;C等位基因频率为33％ （66/200）,T等位基因频率为67％（134/200）.两组分布比较,差异均无统计学意义（P＞0.05）.（5）rs11196205位点在GDM组及对照组中均以GG基因型为主,GDM组GG型频率为99％ （99/100）,CC型频率为1％ （1/100）;G等位基因频率为99％ （198/200）,C等位基因频率为1％ （2/200）.对照组GG型频率为100％ （100/100）,CC型频率为0;G等位基因频率为100％ （200/200）,C等位基因频率为0.两组频率分布比较,差异均无统计学意义（P＞0.05）.（6）rs12255372位点在GDM组及对照组中均为GG基因型,GDM组GG型频率为100％ （100/100）,G等位基因频率为100％ （200/200）;对照组GG型频率为100％ （100/100）,G等位基因频率为100％ （200/200）;两组分别比较,差异均无统计学意义（P＞0.05）.（7）对孕妇的年龄、孕周、分娩时BMI、FPG、FINS及TCF7L2基因型进行logistic回归分析,结果发现,TCF7L2基因rs7903146的TT基因型相对于CC±CT基因型的OR值为2.77（95％ CI为1.03～7.57,P＜0.05）,是C等位基因携带者的2.45倍,TT基因型是发生GDM的危险因素.结论 TCF7L2基因rs7903146位点的多态性与GDM孕妇遗传易感性相关,TT基因型可能是GDM发生的危险因素.

Objective To investigate the relationship between single nucleotide polymorphism （SNP） of transcription factor 7-like 2 （TCF7L2） at locus rs7903146,rs290487,rsl1196205,rs 12255372 and genetic susceptibility in women with gestational diabetes mellitus （GDM）.Methods As a case-control study,100 pregnant women with GDM and 100 healthy pregnant women in the Maternal and Children Health Hospital of Jiangxi Province were recruited from January 2010 to July 2013.Clinical parameters,including body mass index （BMI）,fasting insulin （FINS）,fasting plasma glucose （FPG） and homeostatic model assessment-insulin resistance index （HOMA-IR） were measured after admission to hospital.Allelespecific PCR was used to analyze the SNP of TCF7L2 at locus rs7903146,rs290487,rs11196205,rs12255372.Results （1）The BMI,FPG,FINS and HOMA-IR in GDM group were（27.4±3.0） kg/m2,（5.6±1.0） mmol/L,（6.2±3.4） mU/L and 1.8± 1.0,and were （24.2±2.9） kg/m2,（5.3±0.8） mmol/L,（4.5±2.8） mU/L,1.2± 0.8 in the control group,respectively.The differences had statistically significance （P＜0.05）.（2）The SNP of TCF7L2 gene,locus rs7903146 were CC,CT and TT genotype; the SNP of locus rs290487 were CC,CT and TT genotype; and the SNP of locus rs1 1196205 were GG and CC genotype; while the SNP of locus rs12255372 was GG genotype.（3）The distribution frequencies of genotype CC,CT and TT at locus rs7903146 in the GDM group were 40％ （40/100）,36％ （36/100） and 24％ （24/100）,respectively.While in the control group,they were 55％ （55/100）,38％ （38/100） and 7％ （7/100）,respectively.The frequencies of C and T allele of rs7903146 were 58％and 42％ in the GDM group,and in the control group they were 74％ （148/200） and 26％ （52/200）.The differences of genotype distribution and C/T allele frequency of rs7903146 between the two groups were statistically significant （P＜0.05）.（4）The distribution frequencies of genotype CC,CT and TT at locus rs290487 in the GDM group were 12 ％ （12/100）,36 ％ （36/100） and 52％ （52/100）,and were 16％ （16/100）,34％ （34/100） and 50％ （50/100） in the control group.The frequencies of C and T allele of rs290487 were 30％ （60/200） and 70％ （140/200） in the GDM group,and were 33％ （66/200） and 67％ （134/200） in the control group.There was no difference of genotype distribution and C/T allele frequency of rs290487 between the two groups （P＞0.05）.（5）The distribution frequencies of genotype GG and CC at locus rs1 1196205 in the GDM group were 99％ （99/100） and 1％ （1/ 100）,while those in the control group were 100％（100/100） and 0％.The frequency of G and C allele of rs1 1196205 were 99％（198/200） and 1％（2/200） in the GDM group,while in the control group were 100％ （200/200） and 0.There was no difference of genotype distribution and G/C allele frequency of rs11196205 between the two groups （P＞0.05）.（6）The distribution frequencies of genotype GG at locus rs12255372 were 100％（100/100） in both the GDM group and the control group.The frequencies of G allele of rs12255372 were 100％ （200/200） in both the GDM group and the control group.There was no difference of genotype distribution and G allele frequency of rs12255372 between the two groups （P＞0.05）.（7）After adjusting for age,gestational age,BMI,FPG and FINS,pregnant women with TT genotype at locus rs7903146 were more likely to have hyperglycemia compared with the C allele carriers （OR=2.77,95％ CI：1.03-7.57,P＜0.05）.Conclusions The polymorphism of locus rs7903146 in TCF7L2 gene may be associated with genetic susceptibility in women with GDM.TT genotype is likely to be risk factor in the pathogenesis of GDM.