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Association of PGC-1α gene with type 2 diabetes in three unrelated endogamous groups of North-West India (Punjab): a case-control and meta-analysis study

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Abstract

PGC-1α (Peroxisome proliferator-activated receptor gamma, coactivator 1 alpha) plays a key role in glucose homeostasis inside liver and muscle. The impact of six polymorphisms of PGC-1α with Type 2 Diabetes (T2D) susceptibility was evaluated on 1125 samples comprising of 554 T2D cases and 571 controls among three endogamous groups (Bania, Brahmin and Jat Sikh) of North-West India (Punjab). Single-locus analysis showed a significant differential pattern of genetic association of PGC-1α among studied groups emphasizing the role of ethnicity towards disease susceptibility. Haplotypes G-A-G-G-C-C in Bania group; G-G-G-G-C-A in Brahmin; G-A-A-G-T-C, G-G-G-G-T-C in Jat Sikh groups conferred ~ two to fivefold increased T2D risk. Intriguingly, the haplotype combination G-A-G-G-C-C provided T2D risk in Banias whereas it played a protective role in Brahmins reflecting the role of ethnic heterogeneity. In the secondary structure prediction of mRNA, slight free energy change along with structural changes was observed between the wild and variant allele of rs3736265, rs8192678 and rs2970847 loci. Meta-analyses conducted on rs8192678 and rs2970847 variants illustrated the overall effect of minor alleles providing a higher risk for the T2D development. Divergence in genetic variants and haplotype combinations associated with T2D risk among studied groups is inferred from the present dataset, which strongly highlights the combinatorial effect of diverse ethnic background of the population under study with genetics towards susceptibility to complex diseases like T2D.

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Acknowledgements

The financial assistance to Sharma R. by ICMR is acknowledged. Financial support under the DBT through project grant: BT/PR8846/MED/12/327/2007 (DBT, India) to Bhanwer AJS at Guru Nanak Dev University, Amritsar is highly acknowledged.

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Authors and Affiliations

  1. Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India

    Rubina Sharma, Kawaljit Matharoo & A. J. S. Bhanwer

  2. Heart Station and Diabetes Clinic, Amritsar, India

    Rohit Kapoor

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  1. Rubina Sharma
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  2. Kawaljit Matharoo
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  4. A. J. S. Bhanwer
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Correspondence to Kawaljit Matharoo.

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

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Supplementary material 1 (DOCX 14 KB)

438_2017_1385_MOESM2_ESM.tif

Supplementary Figure 1: Evaluation of publication bias of PGC-1α (Gly482Ser) rs8192678 polymorphism using a funnel plot. The horizontal line in the funnel plot indicates the random effects summary estimate, while the sloping lines indicate the expected 95% CIs for a given standard error, assuming no heterogeneity between studies. Each circle represents a study (TIF 70 KB)

438_2017_1385_MOESM3_ESM.tif

Supplementary Figure 2: Evaluation of publication bias of PGC-1α (Thr394Thr) rs2970847 polymorphism using a funnel plot. The horizontal line in the funnel plot indicates the random effects summary estimate, while the sloping lines indicate the expected 95% CIs for a given standard error, assuming no heterogeneity between studies. Each circle represents a study (TIF 69 KB)

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Sharma, R., Matharoo, K., Kapoor, R. et al. Association of PGC-1α gene with type 2 diabetes in three unrelated endogamous groups of North-West India (Punjab): a case-control and meta-analysis study. Mol Genet Genomics 293, 317–329 (2018). https://doi.org/10.1007/s00438-017-1385-2

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