Identification of Genetic Variants of Gestational Diabetes in South Indians

Kanthimathi, Sekar; Chidambaram, Manickam; Liju, Samuel; Bhavadharini, Balaji; Bodhini, Dhanasekaran; Prakash, Visvanathan Gnana; Amutha, Anandakumar; Bhavatharini, Aruyerchelvan; Anjana, Ranjit Mohan; Mohan, Viswanathan; Radha, Venkatesan

doi:10.1089/dia.2014.0349

Cited by 22 publications

(14 citation statements)

References 37 publications

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“…In addition, there was no significant association between the other two SNPs (rs7754840 and rs1470579) and GDM risk in our study. Consistent with our findings, another study in pregnant Chinese women found no significant association between rs7754840 and GDM risk 18 , whereas studies in Korean, Caucasian and South Indian populations showed significant associations between rs7754840 and GDM risk 12,16,23 . This discrepancy could be due to differences in ethnicities, sample sizes and diagnostic criteria for GDM.…”

Section: Discussionsupporting

confidence: 90%

Association of rs10830962 polymorphism with gestational diabetes mellitus risk in a Chinese population

Xie

Chen

Zhang

et al. 2019

Sci Rep

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To date, only three polymorphisms (rs10830962, rs7754840 and rs1470579) are included in the genome-wide association study Catalog ( www.ebi.ac.uk/gwas ). However, the available evidence is limited in pregnant Chinese women. We aimed to explore the associations of three polymorphisms (rs10830962, rs7754840 and rs1470579) with GDM risk in a Chinese population. We conducted a case-control study (964 GDM cases and 1,021 controls) to evaluate the associations of these polymorphisms with GDM risk. A logistic regression model was used to calculate odds ratios (ORs) and their confidence intervals (CIs). After adjustment for age, prepregnancy BMI, parity, abnormal pregnancy history and family history of diabetes, the minor allele of rs10830962 (C > G) demonstrated a significant association with an increased risk of GDM (OR = 1.16, 95% CI = 1.02–1.31, P = 0.029 in the additive model). However, no significant association was observed between the other two polymorphisms and GDM. Subsequent functional annotation shows that rs10830962 is located in the regulatory elements of pancreatic islets, alters the binding affinity of motifs and regulates SNORA8 expression. Our findings demonstrate that rs10830962 is associated with an increased risk of GDM in the Chinese population. Further functional characterization is warranted to uncover the mechanism of the genotype-phenotype association.

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Section: Discussionsupporting

confidence: 90%

Association of rs10830962 polymorphism with gestational diabetes mellitus risk in a Chinese population

Xie

Chen

Zhang

et al. 2019

Sci Rep

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“…DNA was extracted from frozen and stored buffy coats using (QIAGEN Autopure LS kits. Six SNPs previously associated with GDM or T2D in India [ 21 , 22 , 26 , 27 , 30 ] (Additional file 2 : Table S1) and 79 SNPs previously associated with T2D in Europe and elsewhere from GWAS studies up to 2012 (some of these also with GDM risk from candidate gene studies in GDM populations) were genotyped in the present study (Additional file 2 : Table S1) [ 14 ] on a Sequenom Mass ARRAY Platform (Sequenom San Diego, CA, USA) PLEX using MALDI-TOF mass spectrometer [ 31 ] or Taqman allelic discrimination assays using an ABI Prism 7900 sequence detection system (Applied Biosystems, Foster City, CA, USA). Genotyping was performed at the Lund University Diabetes Centre, Sweden after obtaining permission from ICMR (dated 21 october 2010 and Office of Drugs Controller General (India)(dated 14/12/2010).…”

Section: Methodsmentioning

confidence: 99%

“…However, genetic studies of GDM in India are scarce. The SNPs rs7754840 and rs7756992 in the CDKAL1 gene were associated with GDM in South Indian women [ 26 ], while variants in the HMG20A (rs7178572) and HNF4A (rs4812829) genes were associated with both GDM and T2D [ 27 ]. The aim of the present study was to investigate whether a panel of known variants previously associated with GDM and T2D in Indian and European populations are associated with GDM in Punjabi women.…”

Section: Introductionmentioning

confidence: 99%

Association between genetic risk variants and glucose intolerance during pregnancy in north Indian women

et al. 2018

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BackgroundGestational 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.MethodsFive 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.ResultsIn 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.ConclusionsGDM 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.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0380-8) contains supplementary material, which is available to authorized users.

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“…To our knowledge, only one Asian GWAS study on GDM in Korean women has been published . Few studies have examined the genetic susceptibility to GDM in the Indian population; these included two studies in South Indian women and reported association of variants in the CDKAL1 , HMG20A and HNF4A genes with GDM . It is quite possible that the genetic background contributing to GDM differs between women of North Indian and women of Scandinavian origin and could explain some disparities in the prevalence of GDM.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic and genotypic differences between Indian and Scandinavian women with gestational diabetes mellitus

et al. 2019

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Objective Gestational diabetes mellitus (GDM) is a transient form of diabetes characterized by impaired insulin secretion and action during pregnancy. Population‐based differences in prevalence exist which could be explained by phenotypic and genetic differences. The aim of this study was to examine these differences in pregnant women from Punjab, India and Scandinavia. Methods Eighty‐five GDM/T2D loci in European and/or Indian populations from previous studies were assessed for association with GDM based on Swedish GDM criteria in 4018 Punjabi Indian and 507 Swedish pregnant women. Selected loci were replicated in Scandinavian cohorts, Radiel (N = 398, Finnish) and STORK/STORK‐G (N = 780, Norwegian). Results Punjabi Indian women had higher GDM prevalence, lower insulin secretion and better insulin sensitivity than Swedish women. There were significant frequency differences of GDM/T2D risk alleles between both populations. rs7178572 at HMG20A, previously associated with GDM in South Indian and European women, was replicated in North Indian women. The T2D risk SNP rs11605924 in the CRY2 gene was associated with increased GDM risk in Scandinavian but decreased GDM risk in Punjabi Indian women. No other overlap was seen between GDM loci in both populations. Conclusions Gestational diabetes mellitus is more common in Indian than Swedish women, which partially can be attributed to differences in insulin secretion and action. There was marked heterogeneity in the GDM phenotypes between the populations which could only partially be explained by genetic differences.

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Identification of Genetic Variants of Gestational Diabetes in South Indians

Abstract: The rs7754840 and rs7756992 SNPs of the CDKAL1 gene were found to be associated with GDM in this south Indian population. This is the first study describing genetic susceptibility of GDM in Asian Indians.

Cited by 22 publications

References 37 publications

Association of rs10830962 polymorphism with gestational diabetes mellitus risk in a Chinese population

Association of rs10830962 polymorphism with gestational diabetes mellitus risk in a Chinese population

Association between genetic risk variants and glucose intolerance during pregnancy in north Indian women

Phenotypic and genotypic differences between Indian and Scandinavian women with gestational diabetes mellitus

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