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Association of recently identified type 2 diabetes gene variants with Gestational Diabetes in Asian Indian population

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Abstract

Earlier studies have provided evidence that the gestational diabetes mellitus (GDM) and Type 2 diabetes mellitus (T2DM) share common genetic background. A recent genome wide association study (GWAS) showed a strong association of six novel gene variants with T2DM among south Asians but not with Europeans. The aim of this study was to investigate whether these variants that confer susceptibility to T2DM in Asian Indian population also correlate with GDM in Asian Indian population. In addition to these novel variants, three T2DM associated SNPs that were previously identified by GWAS in Caucasian populations, which also showed association with T2DM in south Indian population in our previous study were also evaluated for their susceptibility to GDM in our population. The study groups comprised unrelated pregnant women with GDM (n = 518) and pregnant women with normal glucose tolerance (NGT) (n = 1220). A total of nine SNPs in or near nine loci, namely AP3S2 (rs2028299), BAZ1B (rs12056034), CDKN2A/B (rs7020996), GRB14 (rs3923113), HHEX (rs7923837), HMG20A (rs7178572), HNF4A (rs4812829), ST6GAL1 (rs16861329) and VPS26A (rs1802295) were genotyped using the MassARRAY system. Among these nine SNPs that previously showed an association with T2DM in Asian Indians, HMG20A (rs7178572) and HNF4A (rs4812829) gene variants showed a significant association with GDM. The risk alleles of rs7178572 in HMG20A and rs4812829 in HNF4A gene conferred 1.24 and 1.28 times higher risk independently and about 1.44 and 1.97 times increased susceptibility to GDM for one and two risk genotypes, respectively. We report that the HMG20A (rs7178572) and HNF4A (rs4812829) variants that have previously shown a strong association with T2DM in Asian Indians also contributes significant risk to GDM in this population. This is the first report of the association of HMG20A (rs7178572) and HNF4A (rs4812829) variants with GDM.

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Acknowledgements

This study was supported by funding from MDRF Innovative Research Fund (MIRF) from the Madras Diabetes Research Foundation, Chennai, India. We thank Balaji Bhavadharini for the sample collection.

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Author notes

  1. Manickam Chidambaram

    Present address: Division of Experimental Genetics, Sidra Medical and Research Center, Out-Patient Clinic, C6-73003, PO Box 26999, Al Luqta Street, Education City North Campus, Qatar Foundation, Doha, Qatar

Authors and Affiliations

  1. Madras Diabetes Research Foundation, No. 4, Conran Smith Road, Gopalapuram, Chennai, India

    Sekar Kanthimathi, Manickam Chidambaram, Dhanasekaran Bodhini, Samuel Liju, Ranjit Mohan Anjana, Viswanathan Mohan & Venkatesan Radha

  2. SRC Diabetes Care Centre, Erode, India

    Aruyerchelvan Bhavatharini

  3. Seethapathy Clinic and Hospital, Chennai, India

    Ram Uma

  4. Dr. Mohan’s Diabetes Specialities Centre, WHO Collaborating Centre for Non Communicable Diseases Prevention and Control, Chennai, India

    Ranjit Mohan Anjana & Viswanathan Mohan

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  1. Sekar Kanthimathi
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  2. Manickam Chidambaram
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Correspondence to Venkatesan Radha.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional ethics committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Kanthimathi, S., Chidambaram, M., Bodhini, D. et al. Association of recently identified type 2 diabetes gene variants with Gestational Diabetes in Asian Indian population. Mol Genet Genomics 292, 585–591 (2017). https://doi.org/10.1007/s00438-017-1292-6

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