Abstract
The recent observations that Peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1A) is responsible for the induction of reactive oxygen species (ROS) detoxifying agents and that ROS triggers insulin resistance, support the role that this gene could play in the onset of Type 2 diabetes mellitus (T2DM). Two PGC1A variants Thr394Thr (rs2970847) and Gly482Ser (rs8192673) were genotyped in 822 subjects (351 T2DM cases and 471 controls) from two North Indian populations, represented as Group 1 (Kashmir population) and Group 2 (Punjab and Jammu population). Both Groups 1 and 2 showed a significant association of Thr394Thr variant with T2DM after applying Bonferroni corrections (P = 0.001 and 0.012, respectively). Logistic regression analysis for Thr394Thr susceptible genotypes together (rs2970847 G/A and A/A) conferred a 1.89-(95%CI 1.25–2.85) fold higher risk for T2DM in Group 1 and 1.81-(95%CI 1.19–2.78) fold risk in Group 2. The susceptible, Ser482 (rs8192673 G/A and A/A) genotypes, gave a 2.04 (95%CI 1.47–3.03) fold higher risk for T2DM in Group 1. Mitochondrial genotype backgrounds observed in association with T2DM (Bhat et al. 2007), when studied in combination with PGC1A variants, showed an increased prevalence in controls with mt10398G and 16189T along with G/G genotype background at the two polymorphic loci of PGC1A. These observations suggest that the two genotype backgrounds together could provide protection against T2DM.
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Acknowledgments
The authors acknowledge the support provided by UGC, India to NCAHG and to the Centre for Advanced Studies, School of Life Sciences, JNU. Authors appreciate the critical reading done by Dr. Dheeraj Malhotra and the suggestions given. The fellowship of CSIR to A. Bhat, A. Koul, S. Sharma, and of UGC to E. Rai is also acknowledged.
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An erratum to this article is available at http://dx.doi.org/10.1007/s00439-008-0464-1.
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Bhat, A., Koul, A., Rai, E. et al. PGC-1α Thr394Thr and Gly482Ser variants are significantly associated with T2DM in two North Indian populations: a replicate case-control study. Hum Genet 121, 609–614 (2007). https://doi.org/10.1007/s00439-007-0352-0
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DOI: https://doi.org/10.1007/s00439-007-0352-0