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Interactive role of endothelial nitric oxide synthase gene polymorphisms in T2D with CAD and CAD patients of Punjab (North-West India)

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Abstract

Dysregulation of endothelial nitric oxide synthase (eNOS) activity causes the reduction in the production of nitric oxide (NO) which is an early indicator of type 2 diabetes (T2D) and cardiovascular complications. The present study evaluates the association of −786 T > C, 894 G > T, and 4a/b polymorphisms of eNOS gene in total of 1223 individuals enrolling 307 coronary artery disease (CAD) cases, 486 T2D cases with (n = 170) and without (n = 316) CAD as the secondary macrovascular complication, and 430 healthy controls from Punjab (North-West India). Genotyping of −786 T > C and 894 G > T polymorphisms was done with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the genotyping of 4a/b insertion/deletion polymorphism was done by PCR. The minor allele frequency (MAF) of −786 T > C polymorphism was higher in CAD (21.8 %), T2D + CAD (22.4 %), and T2D cases (18.4 %) as compared to healthy controls (17.6 %). However, in single-locus analysis, no significant results were obtained for eNOS polymorphisms in any of the studied groups. Significant association of C-b-G haplotype with the risk of both CAD [P = 0.003, odds ratio (OR) = 1.89 (1.04–3.45)] and T2D [P = 0.019, OR = 1.69 (0.92–3.13)] was observed. Diplotype analysis showed that TbG/CbG haplotype combination conferred risk towards CAD and T2D [P = 0.01, OR = 2.04 (1.18–3.57); P = 0.006, OR = 2.13 (1.22–3.57), respectively]. Furthermore, phenotypic parameters like waist circumference, high-density lipoprotein, and waist to height ratio are significantly associated with 894 G > T genotypes among CAD patients. In conclusion, the eNOS polymorphisms did not provide any conclusive result individually; however, their interactive effect gives some insights towards eNOS role in the population of Punjab.

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Acknowledgments

The financial assistance to Kaur R by UGC is acknowledged. The financial assistance under the scheme of “Centre with Potential for Excellence in Particular Area” through grant number F.8-2/2008 (NS/PE; UGC, India) and “University with Potential for Excellence” through grant number F.14-2/2008 (NS/PE; UGC, India) to Bhanwer AJS at Guru Nanak Dev University, Amritsar, is humbly acknowledged.

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    1. Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, 143005, India

      Ramandeep Kaur, Kawaljit Matharoo, Priyanka Raina, Ruhi Sikka & A. J. S. Bhanwer

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    1. Ramandeep Kaur
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    Correspondence to Kawaljit Matharoo or A. J. S. Bhanwer.

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    It is declared that there is no conflict of interest of authors and the research work is entirely for academic purpose and no competing financial interests exist.

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    Priyanka Raina and Ruhi Sikka contributed equally to this work.

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    Kaur, R., Matharoo, K., Raina, P. et al. Interactive role of endothelial nitric oxide synthase gene polymorphisms in T2D with CAD and CAD patients of Punjab (North-West India). Int J Diabetes Dev Ctries 37, 286–297 (2017). https://doi.org/10.1007/s13410-016-0503-8

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