Institut National de la Santé et de la Recherche Médicale, Centre de Recherche en Epidémiologie et Santé des Populations, Université Paris-Sud, Unité Mixte de Recherche en Santé 1018, F-94807 Villejuif, France.
J Clin Endocrinol Metab. 2011 Oct;96(10):E1656-60. doi: 10.1210/jc.2011-0381. Epub 2011 Jul 27.
The protective role of the Ala allele in the Pro12Ala polymorphism of PPARγ on type 2 diabetes has been well established but not confirmed in the context of pregnancy, for gestational diabetes, a known predictor of later type 2 diabetes onset. Another PPARγ polymorphism, the C1431T, is in strong linkage disequilibrium with Pro12Ala and has been shown to be associated with body weight, but its association with diabetes is controversial.
In 1708 women of the EDEN mother-child cohort, the PPARγ Pro12Ala and C1431T polymorphisms were genotyped and analyzed in association with maternal prepregnancy body mass index, obesity before pregnancy, and gestational diabetes, separately and also combined in haplotypes.
The prevalence of obesity was significantly higher in mothers with the Ala/Ala genotype compared with carriers of the Pro allele (35 vs. 9%, P < 0.0001), but there was no cases of gestational diabetes in Ala/Ala mothers. Mothers homozygous for the T allele of C1431T were also more obese (24 vs. 9%, P = 0.035), and three times more had gestational diabetes (18 vs. 6%, P = 0.044). Frequencies of haplotypes for these two single-nucleotide polymorphisms differed significantly in mothers with and without gestational diabetes; in comparison with the Pro-C haplotype, the Pro-T haplotype conferred the highest risk [odds ratio (95% CI) = 1.89 (1.05-3.40)], and the Ala-C the lowest risk [odds ratio (95% CI) = 0.12 (0.52-1.70)].
These results from a haplotype analysis, show for the first time that genetic variations in the PPARγ gene could play a role in the susceptibility to develop gestational diabetes.
PPARγ 基因 Pro12Ala 多态性中的 Ala 等位基因对 2 型糖尿病具有保护作用，这一作用在妊娠期间发生的妊娠期糖尿病中已得到充分证实，因为后者是 2 型糖尿病发病的已知预测因素。另一种 PPARγ 多态性 C1431T 与 Pro12Ala 紧密连锁，并且与体重有关，但它与糖尿病的关系存在争议。
在 EDEN 母婴队列的 1708 名女性中，分别分析了 PPARγ Pro12Ala 和 C1431T 多态性与母亲孕前体重指数、孕前肥胖和妊娠期糖尿病的关系，并分别以单体型和组合单体型进行了分析。
Ala/Ala 基因型母亲的肥胖患病率明显高于携带 Pro 等位基因的母亲（35% vs. 9%，P < 0.0001），但 Ala/Ala 母亲无一例发生妊娠期糖尿病。C1431T 中 T 等位基因纯合的母亲也更肥胖（24% vs. 9%，P = 0.035），并且有妊娠期糖尿病的风险增加三倍（18% vs. 6%，P = 0.044）。在患有和不患有妊娠期糖尿病的母亲中，这两个单核苷酸多态性的单体型频率有显著差异；与 Pro-C 单体型相比，Pro-T 单体型的风险最高[比值比（95%可信区间）= 1.89（1.05-3.40）]，而 Ala-C 单体型的风险最低[比值比（95%可信区间）= 0.12（0.52-1.70）]。
这些单体型分析的结果首次表明，PPARγ 基因的遗传变异可能在发生妊娠期糖尿病的易感性中起作用。
