common variants in crp and lepr influence high sensitivity c-reactive protein levels in north indians常见的变体c反应蛋白和lepr影响灵敏度高c反应蛋白水平在北印度人.pdfVIP

Common Variants in CRP and LEPR Influence High Sensitivity C-Reactive Protein Levels in North Indians 1 1 1 1 1 Anubha Mahajan , Rubina Tabassum , Sreenivas Chavali , Om Prakash Dwivedi , Ganesh Chauhan , 2 3 1 Saurabh Ghosh , Nikhil Tandon *, Dwaipayan Bharadwaj * 1 Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, India, 2 Human Genetics Unit, Indian Statistical Institute, Kolkata, India, 3 Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, India Abstract Background: High sensitivity C-reactive protein (hsCRP) levels are shown to be influenced by genetic variants in Europeans; however, little is explored in Indian population. Methods: Herein, we comprehensively evaluated association of all previously reported genetic determinants of hsCRP levels, including 18 cis (proximal to CRP gene) and 73 trans-acting (distal to CRP gene) variants in 4,200 North Indians of Indo-European ethnicity. First, we evaluated association of 91 variants from 12 candidate loci with hsCRP levels in 2,115 North Indians (1,042 non-diabetic subjects and 1,073 patients with type 2 diabetes). Then, cis and trans-acting variants contributing maximally to hsCRP level variation were further replicated in an independent 2,085 North Indians (1,047 patients with type 2 diabetes and 1,038 non-diabetic subjects). Results: We found association of 12 variants from CRP, LEPR, IL1A, IL6, and IL6R with hsCRP levels in non-diabetic subjects. However, only rs3093059-CRP [b = 0.33, P = 9.6 61025] and the haplotype harboring rs3093059 risk allele [b = 0.32 mg/mL, P = 1.4