Dataset Information

Relationship between rs854560 PON1 Gene Polymorphism and Tobacco Smoking with Coronary Artery Disease.

ABSTRACT: Paraoxonase-1 (PON1) is the antioxidant marker of high-density lipoproteins protecting against atherosclerosis and coronary artery disease (CAD) phenotype. The purpose of the present study was to determine whether the PON1 gene rs854560 polymorphism (163T>A) is associated with CAD in Polish population. rs854560 was genotyped in 494 subjects: 248 patients with premature CAD and 246 blood donors as a control. We found that the risk of CAD was significantly higher in TT homozygotes than in A allele carriers (OR?=?1.87, p = 0.041). The synergistic effect between the TT genotype and cigarette smoking was observed (SIM?=?9.81; SI?=?14.70). The relative increase in risk from interaction between factors was over 37 (RERI?=?36.13). The PON1 polymorphism did not modulate the risk of CAD in response to exposure to other traditional risk factors. In conclusion, the rs854560 polymorphism may modulate the risk of CAD in response to cigarette smoking in Polish population. Carriers of TT genotype seem to be particularly at risk of CAD, when exposed to cigarette smoking.

SUBMITTER: Iwanicka J

PROVIDER: S-EPMC5651137 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Relationship between rs854560 <i>PON1</i> Gene Polymorphism and Tobacco Smoking with Coronary Artery Disease.

Iwanicka Joanna J Iwanicki Tomasz T Niemiec Paweł P Nowak Tomasz T Krauze Jolanta J Grzeszczak Władysław W Górczyńska-Kosiorz Sylwia S Ochalska-Tyka Anna A Żak Iwona I

Disease markers 20170929

Paraoxonase-1 (PON1) is the antioxidant marker of high-density lipoproteins protecting against atherosclerosis and coronary artery disease (CAD) phenotype. The purpose of the present study was to determine whether the <i>PON1</i> gene rs854560 polymorphism (163T>A) is associated with CAD in Polish population. rs854560 was genotyped in 494 subjects: 248 patients with premature CAD and 246 blood donors as a control. We found that the risk of CAD was significantly higher in TT homozygotes than in A ...[more]

PMID: 29118461

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Project description:BackgroundObservational and experimental studies have thus far been unable to resolve whether the CYBA C242T polymorphism is associated with coronary artery disease (CAD). Therefore, we undertook a comprehensive meta-analysis to more precisely evaluate the influence of this polymorphism on CAD and potential biases.MethodsWe screened MEDLINE, Embase, CNKI, Wanfang and CBM up to January 2013 and extracted data from 22 studies with 9,279 CAD patients and 9,349 controls. A random-effects model was exploited to synthesize the inconsistent outcomes of the individual studies, while addressing between-study heterogeneity and publication bias.ResultsThe CYBA C242T polymorphism conformed to Hard-Weinberg Equilibrium for all studies (P>0.05). Overall comparison of the T allele with the C allele produced a non-significant risk estimate for CAD but with striking heterogeneity (T versus C: P?=?0.87, OR?=?0.99, 95%CI 0.89-1.11, P(heterogeneity)<0.0001, I²?=?67.8%). However, subgroup analysis by ethnicity documented that the T allele carriers had a marginal risk increase (21%) of CAD among Caucasians (recessive genetic model: P?=?0.05, 95%CI 1.00-1.46, P(heterogeneity)?=?0.15, I²?=?29.1%). Then data were divided into study design, the significance of CAD risk increase was substantially strengthened in matched case-control studies (allele comparison: P?=?0.02, OR?=?1.13, 95%CI 1.02-1.26, P(heterogeneity)?=?0.24, I²?=?21.6%).Further meta-regression analysis identified that a large proportion of heterogeneity was explained by body mass index (BMI) (P?=?0.03, OR?=?1.07, 95%CI 1.01-1.15) and study design (P?=?0.03, OR?=?1.30, 95%CI 1.02-1.64).There was no obvious publication bias as verified by funnel plot and Egger's linear regression test (t?=?-0.25, P?=?0.81 for allele comparison).ConclusionTaken together, our results suggested the CYBA C242T polymorphism might be a risk-conferring factor on developing CAD and BMI and study design were probable sources of between-study heterogeneity.

Project description:Coronary artery disease (CAD) is the principal cause of death in patients with nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to investigate whether NAFLD is causally involved in the pathogenesis of CAD. For this, previously reported NAFLD susceptibility genes were clustered and tested for an association with CAD in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis plus the Coronary Artery Disease Genetics (CARDIoGRAMplusC4D) Consortium data set. The role of plasma lipids as a potential mediator was explored by using data from the Global Lipids Genetics Consortium. Statistical analyses revealed that the combination of 12 NAFLD genes was not associated with CAD in 60,801 CAD cases and 123,504 controls (odds ratio [OR] per NAFLD risk allele, 1.0; 95% confidence interval [CI], 0.99-1.00). In a subsequent sensitivity analysis, a positive relationship was observed after exclusion of gene variants that are implicated in NAFLD through impaired very low-density lipoprotein secretion (i.e., microsomal triglyceride transfer protein [MTTP], patatin-like phospholipase domain containing 3 [PNPLA3], phosphatidylethanolamine N-methyltransferase [PEMT], and transmembrane 6 superfamily member 2 [TM6SF2]) (OR, 1.01; 95% CI, 1.00-1.02). Clustering of the excluded genes showed a significant negative relationship with CAD (OR, 0.97; 95% CI, 0.96-0.99). A substantial proportion of the observed heterogeneity between the individual NAFLD genes in relation to CAD could be explained by plasma lipids, as reflected by a strong relationship between plasma lipids and CAD risk conferred by the NAFLD susceptibility genes (r = 0.76; P = 0.004 for low-density lipoprotein cholesterol). Conclusion: NAFLD susceptibility genes do not cause CAD per se. The relationship between these genes and CAD appears to depend to a large extent on plasma lipids. These observations strongly suggest taking plasma lipids into account when designing a new drug to target NAFLD.

Dataset Information

Relationship between rs854560 PON1 Gene Polymorphism and Tobacco Smoking with Coronary Artery Disease.

Publications

Relationship between rs854560 <i>PON1</i> Gene Polymorphism and Tobacco Smoking with Coronary Artery Disease.

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