NDLI: Interleukin-1 Gene Cluster Polymorphisms and Their Association with Coronary Artery Disease: Separate Evidences from the Largest Case-Control Study amongst North Indians and an Updated Meta-Analysis.

Content Provider	Directory of Open Access Journals (DOAJ)
Author	Himanshu Rai Nakul Sinha Sudeep Kumar Ajay Kumar Sharma Suraksha Agrawal
Abstract	Several researchers have reported significant association of numerous single nucleotide polymorphisms (SNPs) residing in the interleukin-1 (IL-1) gene cluster with coronary artery disease (CAD). However, their association status amongst North Indian ancestry (NIA) have never been systematically assessed. Despite a published meta-analysis on this subject, their association status worldwide as well as amongst different major ancestral subgroups still remains unclear. We therefore decided to prospectively test the association of 11 IL-1 gene cluster SNPs with CAD, vide a case-control study amongst a cohort of NIA and attempted to validate our results with the help of an updated meta-analysis of all relevant published association studies. Included studies were segregated into ancestral subgroups and association statuses for each subgroup were determined. A total of 323 cases and 400 healthy, age and sex matched controls belonging to NIA were prospectively enrolled and subsequently genotyped for 11 selected IL-1 gene cluster SNPs. Although results for none of the evaluated IL-1 gene cluster SNPs reached the adjusted level of significance (p<0.0045), clear trends of association were seen for IL1B -511 C>T and IL1RN 86bp VNTR in several of the constructed genetic models (p range = 0.01-0.044 and 0.005-0.034 respectively). The presence of >1, 'T' (minor) allele of IL1B -511 C>T in a genotype seemed to provide protection against CAD (OR = 0.62, p = 0.044), while the presence of >1, 'C' (major) allele seemed to increase the risk of CAD (OR = 1.36, p = 0.041). The minor allele (allele 2) of IL1RN 86bp VNTR and its homozygous genotype (2/2 genotype) also seemed to carry an increased risk for CAD (OR = 1.62, p = 0.005 and OR = 2.25, p = 0.031 respectively). On the other hand, several haplotype combinations constructed out of IL1B and IL1RN gene variants clearly showed statistically significant associations with CAD (p<0.0045). Our meta-analysis was conducted for 8 previously assessed IL-1 SNPs. We included 53 different studies which involved a total sample of 26,210 (13,982 cases and 12,228 controls). Our pooled results concurred with the findings of our case-control study and was not able to deduce any statistically significant associations for any of the 8 studied SNPs (p>0.05). Subgroup analysis, however, yielded interesting results, where significant differences in association statuses were seen for IL1A +4845 G>T, IL1B -511 C>T, IL1RN 86bp VNTR and IL1RN +8006 T>C for select ancestral subgroups. The hints of associations deduced for subjects belonging to NIA in our case-control study for both IL1B -511 C>T and IL1RN 86bp VNTR were duly validated vide significant p values seen for NIA in all three genetic models (OR range = 0.62-0.76, p range = 0.01-0.04 and OR range = 1.51-2.25, p range = 0.004-0.04 respectively). On the other hand, Mixed Ancestry (MA) subgroup carrying IL1B -511 C>T, IL1RN 86bp VNTR or IL1RN +8006 T>C polymorphisms seemed to enjoy significant protection against CAD. A few other ancestral subgroups also demonstrated significant associations for a few of the studied SNPs vide one of the three genetic models. Clinical interpretation of derived results is however recommended.
e-ISSN	19326203
DOI	10.1371/journal.pone.0153480
Journal	PLoS ONE
Issue Number	4
Volume Number	11
Language	English
Publisher	Public Library of Science (PLoS)
Publisher Date	2016-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Medicine Science
Content Type	Text
Resource Type	Article

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