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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 [??=?0.33, P?=?9.6×10??] and the haplotype harboring rs3093059 risk allele [??=?0.32 µg/mL, P?=?1.4×10??/P(perm)?=?9.0×10??] retained significance after correcting for multiple testing. The cis-acting variant rs3093059-CRP had maximum contribution to the variance in hsCRP levels (1.14%). Among, trans-acting variants, rs1892534-LEPR was observed to contribute maximally to hsCRP level variance (0.59%). Associations of rs3093059-CRP and rs1892534-LEPR were confirmed by replication and attained higher significance after meta-analysis [?(meta)?=?0.26/0.22; P(meta)?=?4.3×10??/7.4×10?³ and ?(meta)?=?-0.15/-0.12; P(meta)?=?2.0×10??/1.6×10?? for rs3093059 and rs1892534, respectively in non-diabetic subjects and all subjects taken together].Conclusion
In conclusion, we identified rs3093059 in CRP and rs1892534 in LEPR as major cis and trans-acting contributor respectively, to the variance in hsCRP levels in North Indian population.
SUBMITTER: Mahajan A
PROVIDER: S-EPMC3169613 | biostudies-literature | 2011
REPOSITORIES: biostudies-literature
Mahajan Anubha A Tabassum Rubina R Chavali Sreenivas S Dwivedi Om Prakash OP Chauhan Ganesh G Ghosh Saurabh S Tandon Nikhil N Bharadwaj Dwaipayan D
PloS one 20110908 9
<h4>Background</h4>High sensitivity C-reactive protein (hsCRP) levels are shown to be influenced by genetic variants in Europeans; however, little is explored in Indian population.<h4>Methods</h4>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 fr ...[more]