Please use this identifier to cite or link to this item: http://buratest.brunel.ac.uk/handle/2438/14647
Title: Are C-Reactive Protein Associated Genetic Variants Associated with Serum Levels and Retinal Markers of Microvascular Pathology in Asian Populations from Singapore?
Authors: Dorajoo, R
Li, R
Ikram, MK
Liu, J
Froguel, P
Lee, J
Sim, X
Ong, RT-H
Tay, WT
Peng, C
Young, TL
Blakemore, AIF
Cheng, CY
Aung, T
Mitchell, P
Wang, JJ
Klaver, CC
Boerwinkle, E
Klein, R
Siscovick, DS
Jensen, RA
Gudnason, V
Smith, AV
Teo, YY
Wong, TY
Tai, E-S
Heng, C-K
Friedlander, Y
Keywords: Science & Technology;Multidisciplinary Sciences;Science & Technology - Other Topics;MULTIDISCIPLINARY SCIENCES;CORONARY-HEART-DISEASE;GENOME-WIDE ASSOCIATION;CHRONIC KIDNEY-DISEASE;CARDIOVASCULAR RISK-FACTORS;ATHEROSCLEROSIS RISK;METABOLIC-SYNDROME;VESSEL CALIBER;INFLAMMATION;HEALTH;LOCI
Issue Date: 2013
Publisher: Public Library of Science
Citation: PLOS ONE, 8 (7):(2013)
Abstract: Introduction: C-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations. Methods: Genome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N = 2,434) and Malays (N = 2,542) and South-Asian Indians (N = 2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry. Results: Serum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values #4.761028) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values #0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value #0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value .0.058). Conclusions: Common variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian and South-Asian populations. We did not find a causal link between CRP and retinal measures of microvascular disease.
URI: http://bura.brunel.ac.uk/handle/2438/14647
DOI: http://dx.doi.org/10.1371/journal.pone.0067650
ISSN: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000321341000066&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=f12c8c83318cf2733e615e54d9ed7ad5
ARTN e67650
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000321341000066&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=f12c8c83318cf2733e615e54d9ed7ad5
ARTN e67650
1932-6203
Appears in Collections:Dept of Life Sciences Research Papers

Files in This Item:
File Description SizeFormat 
Fulltext.pdf1.17 MBAdobe PDFView/Open


Items in BURA are protected by copyright, with all rights reserved, unless otherwise indicated.