Association between genetic risk variants and glucose intolerance during pregnancy in north Indian women.
Association between genetic risk variants and glucose intolerance during pregnancy in north Indian women.
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DOI：
10.1186/s12920-018-0380-8
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发表时间：
2018-08-08
影响因子：
2.7
通讯作者：
Prasad RB
中科院分区：
文献类型：
--
作者：
Arora GP;Almgren P;Brøns C;Thaman RG;Vaag AA;Groop L;Prasad RB
妊娠糖尿病（GDM）在印度是一个比世界上许多其他地方更常见的问题，但目前还不知道这是由于独特的环境因素还是独特的遗传背景。为了解决这个问题，我们研究了与高加索人GDM和2型糖尿病（T2 D）相关的相同遗传变异是否也与北印度妇女的GDM相关。通过75 g口服葡萄糖耐量试验（OGTT）对来自旁遮普的5100名孕龄24-28周的孕妇进行了研究。根据WHO 1999和2013标准诊断GDM。在Sequenom平台上或使用Taqman分析法对4018名女性的DNA进行基因分型，79个先前与T2 D和血糖性状相关的单核苷酸多态性（SNP）（其中12个也与GDM相关）和6个来自印度人群的先前T2 D相关性（一些也与欧洲人相关）。为了支持先前在高加索GDM中的发现，在印度妇女中，KCJN 11和GRB 14位点的SNP与GDM 1999风险名义上相关（均p = 0.02）。值得注意的是，CENTD 2附近的变体rs 1552224、ADCY 5中的rs 11708067和ADCY 2基因中的rs 11605924的T2 D风险等位基因与GDM的保护相关，无论应用的标准如何（p < 0.025）。COBLL 1附近的SNP rs7607980（p = 0.0001）、GRB 14附近的SNP rs 13389219（p = 0.026）和GIPR基因中的SNP rs 10423928（p = 0.012）以及这些先前显示的胰岛素抵抗基因座的遗传风险评分（GRS）与HOMA 2-IR定义的胰岛素抵抗相关，并显示出GDM的趋势。GRS由3个胰岛素分泌位点组成，与胰岛素分泌相关，但与GDM无关。来自印度北方旁遮普妇女的GDM显示出遗传成分，似乎由胰岛素抵抗和分泌驱动，部分与世界其他地区的GDM相同。在欧洲研究中发现的大多数先前的T2 D基因座与印度北部的GDM不相关，这表明不同的遗传病因学或替代地，在其中鉴定相关SNP的人群与北方印度妇女之间的连锁不平衡（LD）结构的差异。有趣的是，一些T2 D风险变异实际上表明这些印度妇女对GDM具有保护作用。本文的在线版本（10.1186/s12920-018-0380-8）包含补充材料，可供授权用户使用。
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. 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. 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. 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. The online version of this article (10.1186/s12920-018-0380-8) contains supplementary material, which is available to authorized users.
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影响因子：
7.7
作者：
Kwak SH;Kim SH;Cho YM;Go MJ;Cho YS;Choi SH;Moon MK;Jung HS;Shin HD;Kang HM;Cho NH;Lee IK;Kim SY;Han BG;Jang HC;Park KS
通讯作者：
Park KS
影响因子：
8.2
作者：
Cho, Y. M.;Kim, T. H.;Jang, H. C.
通讯作者：
Jang, H. C.
影响因子：
5.8
作者：
Lauenborg, Jeannet;Grarup, Niels;Hansen, Torben
通讯作者：
Hansen, Torben
影响因子：
5.8
作者：
Arora, Geeti P.;Thaman, Richa G.;Vaag, Allan A.
通讯作者：
Vaag, Allan A.
影响因子：
5.4
作者：
Kanthimathi, Sekar;Chidambaram, Manickam;Radha, Venkatesan
通讯作者：
Radha, Venkatesan