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Genetic association of pro-inflammatory cytokine gene polymorphisms with coronary artery disease (CAD) in a North Indian population

Cytokines regulate the expression of inflammatory molecules which destabilize the atheromatic plaques. This study focuses on studying the association of inflammatory cytokine polymorphisms like TNF-α −308 (G/A), TNF-β +252 (A/G), IL-6 −174 (G/C) and IL-6 −597 (G/A), and IFN-ɣ +874 (T/A) with coronar...

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Published in:Gene 2017-09, Vol.628, p.301-307
Main Authors: Mastana, Sarabjit, Prakash, Swayam, Akam, Elizabeth C., Kirby, Melissa, Lindley, Martin R., Sinha, Nakul, Agrawal, Suraksha
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container_title Gene
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description Cytokines regulate the expression of inflammatory molecules which destabilize the atheromatic plaques. This study focuses on studying the association of inflammatory cytokine polymorphisms like TNF-α −308 (G/A), TNF-β +252 (A/G), IL-6 −174 (G/C) and IL-6 −597 (G/A), and IFN-ɣ +874 (T/A) with coronary artery disease (CAD) among north Indian patients. 143 CAD and 137 normal healthy controls were recruited in this study. DNA extraction was carried out by high salting out method. TNF-α −308 (G/A) (rs1800797), TNF-β +252 (A/G) (rs909253), IL-6 −174 (G/C) (rs1800795), IL6 −597 (G/A) (rs1800797), and IFN-ɣ +874 (T/A) (rs2430561) SNPs were genotyped by TaqMan®SNP genotyping assays. Different statistical analyses were performed using SPSS v 22.0 and SNPStats. p≤0.05 was considered significant. Significant risk association with CAD was found for TNF-α −308 (G/A) “A” allele (OR=5.6, CI 1.8–17.4, p=0.001) and TNF-β +252 (A/G) “G” allele (OR=3.4, CI=1.9–6.0, p
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This study focuses on studying the association of inflammatory cytokine polymorphisms like TNF-α −308 (G/A), TNF-β +252 (A/G), IL-6 −174 (G/C) and IL-6 −597 (G/A), and IFN-ɣ +874 (T/A) with coronary artery disease (CAD) among north Indian patients. 143 CAD and 137 normal healthy controls were recruited in this study. DNA extraction was carried out by high salting out method. TNF-α −308 (G/A) (rs1800797), TNF-β +252 (A/G) (rs909253), IL-6 −174 (G/C) (rs1800795), IL6 −597 (G/A) (rs1800797), and IFN-ɣ +874 (T/A) (rs2430561) SNPs were genotyped by TaqMan®SNP genotyping assays. Different statistical analyses were performed using SPSS v 22.0 and SNPStats. p≤0.05 was considered significant. Significant risk association with CAD was found for TNF-α −308 (G/A) “A” allele (OR=5.6, CI 1.8–17.4, p=0.001) and TNF-β +252 (A/G) “G” allele (OR=3.4, CI=1.9–6.0, p&lt;0.001). However, no statistical significance was found for IL-6 −174 (G/C) or IL6 −597 (G/A), with CAD. TNF-α −308 (G/A), and TNF-β +252 (A/G) haplotype “GG” “AG” increased CAD risk significantly (GG haplotype, adjusted OR=2.6, CI 1.4–5.0, p=0.003 and AG haplotype OR=8.5, CI 2.2–33.35, p=0.002) after adjustments for age, sex, TC, TG, HDL, APOB, smoking and diet. The present study found significant risk association for TNF-α −308 (G/A), and TNF-β +252 (A/G) genotypes, alleles and haplotypes, with CAD in a North Indian population. •Strong independent effects of TNF-α −308 and TNF-β +252 loci on CAD risk•Haplotype AG increases CAD risk by 8.5 times in North Indian population.•IL-6 polymorphisms have no significant effect on CAD in this population.•Genetic analysis of these and other inflammatory genes in CAD are warranted.</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/j.gene.2017.07.050</identifier><identifier>PMID: 28739396</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Alleles ; Analysis of Variance ; Biomarkers ; CAD ; Case-Control Studies ; Coronary Artery Disease - blood ; Coronary Artery Disease - genetics ; Cytokines - genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; IFN-ɣ + 874 (T/A) (rs2430561) ; IL-6 − 174 (G/C) (rs1800795) ; IL6 − 597 (G/A) (rs1800797) ; India ; Male ; Middle Aged ; North India ; Odds Ratio ; Polymorphism, Single Nucleotide ; Risk Factors ; TNF-α − 308 (G/A) (rs1800797) ; TNF-β + 252 (A/G) (rs909253)</subject><ispartof>Gene, 2017-09, Vol.628, p.301-307</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-eb47f7a11d86a5f08ba052852752c80d05249699f2633e690144b3dac30b74353</citedby><cites>FETCH-LOGICAL-c400t-eb47f7a11d86a5f08ba052852752c80d05249699f2633e690144b3dac30b74353</cites><orcidid>0000-0002-9553-4886</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28739396$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mastana, Sarabjit</creatorcontrib><creatorcontrib>Prakash, Swayam</creatorcontrib><creatorcontrib>Akam, Elizabeth C.</creatorcontrib><creatorcontrib>Kirby, Melissa</creatorcontrib><creatorcontrib>Lindley, Martin R.</creatorcontrib><creatorcontrib>Sinha, Nakul</creatorcontrib><creatorcontrib>Agrawal, Suraksha</creatorcontrib><title>Genetic association of pro-inflammatory cytokine gene polymorphisms with coronary artery disease (CAD) in a North Indian population</title><title>Gene</title><addtitle>Gene</addtitle><description>Cytokines regulate the expression of inflammatory molecules which destabilize the atheromatic plaques. 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TNF-α −308 (G/A), and TNF-β +252 (A/G) haplotype “GG” “AG” increased CAD risk significantly (GG haplotype, adjusted OR=2.6, CI 1.4–5.0, p=0.003 and AG haplotype OR=8.5, CI 2.2–33.35, p=0.002) after adjustments for age, sex, TC, TG, HDL, APOB, smoking and diet. 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This study focuses on studying the association of inflammatory cytokine polymorphisms like TNF-α −308 (G/A), TNF-β +252 (A/G), IL-6 −174 (G/C) and IL-6 −597 (G/A), and IFN-ɣ +874 (T/A) with coronary artery disease (CAD) among north Indian patients. 143 CAD and 137 normal healthy controls were recruited in this study. DNA extraction was carried out by high salting out method. TNF-α −308 (G/A) (rs1800797), TNF-β +252 (A/G) (rs909253), IL-6 −174 (G/C) (rs1800795), IL6 −597 (G/A) (rs1800797), and IFN-ɣ +874 (T/A) (rs2430561) SNPs were genotyped by TaqMan®SNP genotyping assays. Different statistical analyses were performed using SPSS v 22.0 and SNPStats. p≤0.05 was considered significant. Significant risk association with CAD was found for TNF-α −308 (G/A) “A” allele (OR=5.6, CI 1.8–17.4, p=0.001) and TNF-β +252 (A/G) “G” allele (OR=3.4, CI=1.9–6.0, p&lt;0.001). However, no statistical significance was found for IL-6 −174 (G/C) or IL6 −597 (G/A), with CAD. TNF-α −308 (G/A), and TNF-β +252 (A/G) haplotype “GG” “AG” increased CAD risk significantly (GG haplotype, adjusted OR=2.6, CI 1.4–5.0, p=0.003 and AG haplotype OR=8.5, CI 2.2–33.35, p=0.002) after adjustments for age, sex, TC, TG, HDL, APOB, smoking and diet. The present study found significant risk association for TNF-α −308 (G/A), and TNF-β +252 (A/G) genotypes, alleles and haplotypes, with CAD in a North Indian population. •Strong independent effects of TNF-α −308 and TNF-β +252 loci on CAD risk•Haplotype AG increases CAD risk by 8.5 times in North Indian population.•IL-6 polymorphisms have no significant effect on CAD in this population.•Genetic analysis of these and other inflammatory genes in CAD are warranted.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28739396</pmid><doi>10.1016/j.gene.2017.07.050</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-9553-4886</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 0378-1119
ispartof Gene, 2017-09, Vol.628, p.301-307
issn 0378-1119
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source ScienceDirect Journals
subjects Adult
Alleles
Analysis of Variance
Biomarkers
CAD
Case-Control Studies
Coronary Artery Disease - blood
Coronary Artery Disease - genetics
Cytokines - genetics
Female
Gene Frequency
Genetic Predisposition to Disease
Genotype
Humans
IFN-ɣ + 874 (T/A) (rs2430561)
IL-6 − 174 (G/C) (rs1800795)
IL6 − 597 (G/A) (rs1800797)
India
Male
Middle Aged
North India
Odds Ratio
Polymorphism, Single Nucleotide
Risk Factors
TNF-α − 308 (G/A) (rs1800797)
TNF-β + 252 (A/G) (rs909253)
title Genetic association of pro-inflammatory cytokine gene polymorphisms with coronary artery disease (CAD) in a North Indian population
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