印度北部女性妊娠期间遗传风险变异与葡萄糖不耐受的相关性。
Association between genetic risk variants and glucose intolerance during pregnancy in north Indian women.
机构信息
Deep Hospital, Ludhiana, Punjab, India.
Department of Clinical Sciences, Clinical Research Centre, Lund University, Malmö, Sweden.
出版信息
BMC Med Genomics. 2018 Aug 8;11(1):64. doi: 10.1186/s12920-018-0380-8.
BACKGROUND
Gestational diabetes (GDM) is a more common problem in India than in many other parts of the world but it is not known whether this is due to unique environmental factors or a unique genetic background. To address this question we examined whether the same genetic variants associated with GDM and Type 2 Diabetes (T2D) in Caucasians also were associated with GDM in North Indian women.
METHODS
Five thousand one hundred pregnant women of gestational age 24-28 weeks from Punjab were studied by a 75 g oral glucose tolerance test (OGTT). GDM was diagnosed by both WHO1999 and 2013 criteria. 79 single nucleotide polymorphisms (SNPs) previously associated with T2D and glycemic traits (12 of them also with GDM) and 6 SNPs from previous T2D associations based on Indian population (some also with European) were genotyped on a Sequenom platform or using Taqman assays in DNA from 4018 women.
RESULTS
In support of previous findings in Caucasian GDM, SNPs at KCJN11 and GRB14 loci were nominally associated with GDM1999 risk in Indian women (both p = 0.02). Notably, T2D risk alleles of the variant rs1552224 near CENTD2, rs11708067 in ADCY5 and rs11605924 in CRY2 genes associated with protection from GDM regardless of criteria applied (p < 0.025). SNPs rs7607980 near COBLL1 (p = 0.0001), rs13389219 near GRB14 (p = 0.026) and rs10423928 in the GIPR gene (p = 0.012) as well as the genetic risk score (GRS) for these previously shown insulin resistance loci here associated with insulin resistance defined by HOMA2-IR and showed a trend towards GDM. GRS comprised of 3 insulin secretion loci here associated with insulin secretion but not GDM.
CONCLUSIONS
GDM in women from Punjab in Northern India shows a genetic component, seemingly driven by insulin resistance and secretion and partly shared with GDM in other parts of the world. Most previous T2D loci discovered in European studies did not associate with GDM in North India, indicative of different genetic etiology or alternately, differences in the linkage disequilibrium (LD) structure between populations in which the associated SNPs were identified and Northern Indian women. Interestingly some T2D risk variants were in fact indicative of being protective for GDM in these Indian women.
背景
妊娠糖尿病（GDM）在印度比在世界上许多其他地区更为常见，但尚不清楚这是由于独特的环境因素还是独特的遗传背景所致。为了解决这个问题，我们研究了在高加索人中与 GDM 和 2 型糖尿病（T2D）相关的相同遗传变异是否也与北印度妇女的 GDM 相关。
方法
对来自旁遮普邦的 5100 名妊娠 24-28 周的孕妇进行了研究，采用 75g 口服葡萄糖耐量试验（OGTT）进行检查。根据 WHO1999 年和 2013 年的标准诊断 GDM。先前与 T2D 和血糖特征相关的 79 个单核苷酸多态性（SNP）（其中 12 个也与 GDM 相关）和 6 个基于印度人群的先前 T2D 关联的 SNP（其中一些也与欧洲人群相关）在 4018 名女性的 DNA 上使用 Sequenom 平台或 Taqman 测定法进行了基因分型。
结果
支持高加索 GDM 的先前发现，在印度女性中，KCJN11 和 GRB14 基因座上的 SNP 与 GDM1999 风险呈名义相关（均为 p=0.02）。值得注意的是，CENTD2 附近的变体 rs1552224、ADCY5 中的 rs11708067 和 CRY2 基因中的 rs11605924 的 T2D 风险等位基因与 GDM 相关，无论应用何种标准均能提供保护（p<0.025）。COBLL1 附近的 rs7607980（p=0.0001）、GRB14 附近的 rs13389219（p=0.026）和 GIPR 基因中的 rs10423928（p=0.012）以及此处与胰岛素抵抗定义的 HOMA2-IR 相关的先前显示的胰岛素抵抗基因座的遗传风险评分（GRS）与 GDM 相关，并且呈趋势。由 3 个胰岛素分泌基因座组成的 GRS 与胰岛素分泌相关，但与 GDM 无关。
结论
来自印度北部旁遮普邦的女性的 GDM 表现出遗传成分，似乎是由胰岛素抵抗和分泌驱动的，并且与世界其他地区的 GDM 部分相关。在欧洲研究中发现的大多数先前的 T2D 基因座与印度北部的 GDM 无关，表明遗传病因不同，或者与先前确定相关 SNP 的人群与印度北部女性之间的连锁不平衡（LD）结构不同。有趣的是，一些 T2D 风险变体实际上表明这些印度女性的 GDM 具有保护作用。
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