Paraoxonase 1 gene polymorphisms contribute to coronary artery disease risk among north Indians

Agrawal, Suraksha; Tripathi, Gaurav; Prajnya, R.; Sinha, Nakul; Gilmour, Ashley; Bush, L.; Mastana, Sarabjit S.

doi:10.4103/0019-5359.55884

Cited by 33 publications

(10 citation statements)

References 39 publications

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“…Our results agreed with earlier studies showing that PON1-55 independently has no consequence on CAD [10, 30, 40]. Contrariwise, a study proposed the protective effect of the M allele of PON1 against CAD [48].…”

Section: Discussionsupporting

confidence: 83%

“…Some of the studies that were accomplished to demonstrate the relationship between the PON1-L55M polymorphism and CAD showed conflicting results [51]. In an Austrian population, it was seen that the L55M polymorphism was linked with CAD [49], whereas studies in other populations showed inconsistent results [30]. Our study showed a negative correlation between the L55M locus and CAD risk, and only the M allele was concluded to be a risk allele.…”

Section: Discussionmentioning

confidence: 59%

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Paraoxonase 1 Gene Polymorphisms (Q192R and L55M) Are Associated with Coronary Artery Disease Susceptibility in Asian Indians

Kaur

Bhatti

Vijayvergiya

et al. 2018

Dubai Diabetes Endocrinol J

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Background: Coronary artery disease (CAD) is a complex metabolic disorder in which lifestyle and genetic factors are known to play key roles in pathogenesis. The paraoxonase 1 (PON1) enzyme has a defensive effect against CAD progression, as it safeguards low-density lipoproteins (LDLs) from oxidative modifications. The most extensively studied genetic variants in the PON1 gene are Q192R and L55M, which have been related with LDL antioxidative activity and risk of CAD. Objective: The present case-control study intended to examine the Q192R and L55M polymorphisms and their association with the risk of CAD patients in north Indians. Methods: A total of 872 subjects (412 CAD patients and 460 controls) were recruited from north India. The PON1 gene was amplified and genotypes were studies using PCR-RFLP. χ² analysis was performed to compare genotype/allele frequencies in patients and controls. Results: The present study indicated abdominal obesity, elevated body mass index, and dyslipidemia with increased levels of total cholesterol and triglycerides as well as reduced high-density lipoprotein cholesterol in CAD subjects compared to healthy controls (p < 0.05). Logistic regression analysis of the data revealed an association of the RR genotype of the Q192R polymorphism with an about 2-fold elevated risk of CAD (OR = 2.23, 95% CI = 1.47–3.37, p = 0.0001). Contrariwise, the L55M polymorphism did not show significant association with CAD (OR = 1.81, 95% CI = 0.66–4.95, p = 0.326). Conclusions: The Q192R polymorphism in the PON1 gene may be a susceptibility gene associated with increased risk of CAD in an Asian Indian population.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 59%

Paraoxonase 1 Gene Polymorphisms (Q192R and L55M) Are Associated with Coronary Artery Disease Susceptibility in Asian Indians

Kaur

Bhatti

Vijayvergiya

et al. 2018

Dubai Diabetes Endocrinol J

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“…Another paper analyzed PON1 192 and 55 polymorphisms in the etiology of CAD. The authors failed to find an association between PON1 55 polymorphism and the onset of cardiovascular disease, but they found that LL genotype and L allele were significant risk factors in the nonsmoker group [16]. Accordingly to this study, Malin et al [17] also have found that in nonsmoking men the LL genotype could represent a genetic risk factor for carotid artery atherosclerotic disease.…”

Section: Discussionmentioning

confidence: 68%

Paraoxonase-1 55 LL Genotype Is Associated with No ST-Elevation Myocardial Infarction and with High Levels of Myoglobin

et al. 2012

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It is well known that serum paraoxonase (PON1) plays an important role in the protection of LDL from oxidation. PON1 55 polymorphism is currently investigated for its possible involvement in cardiovascular diseases. The objective of our study is to verify if PON1 55 polymorphism is associated with risk of acute coronary syndrome (ACS) and with biochemical myocardial ischemia markers, such as troponin I, creatine kinase (CK)-MB, myoglobin, and C-reactive protein. We analysed PON1 55 polymorphism in a total of 440 elderly patients who underwent an ACS episode: 98 patients affected by unstable angina (UA), 207 AMI (acute myocardial infarction) patients affected by STEMI (ST elevation), and 135 AMI patients affected by NSTEMI (no ST elevation). We found that individuals carrying PON1 55 LL genotype are significantly more represented among AMI patients affected by NSTEMI; moreover, the patients carrying LL genotype showed significantly higher levels of myoglobin in comparison to LM + MM carriers patients. Our study suggests that PON1 55 polymorphism could play a role in the pathogenesis of cardiac ischemic damage. In particular, the significant association between PON1 55 LL genotype and the occurrence of a NSTEMI may contribute to improve the stratification of the cardiovascular risk within a population.

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“…For this purpose, previous studies have assessed the interactions between a limited number of coding variants in PON1 and cigarette smoking status on the risk of CHD. However results have been inconclusive [15,16]. For example, a study in the Costa Rican population showed a significant interaction between the rs662 v ariant and smoking status to modify CHD risk [15].…”

Section: Introductionmentioning

confidence: 99%

“…In this study, the C allele at rs662 was reported to increase the risk of CHD in non-smokers only. However, another study conducted in a different ethnic group (Asian-Indians) indicated contrasting results for the same PON1 SNP (rs662), in which the risk allele (C allele) was associated with increased CHD risk among smokers [16]. …”

Section: Introductionmentioning

confidence: 99%

Interaction effects between Paraoxonase 1 variants and cigarette smoking on risk of coronary heart disease in a Singaporean Chinese population

Han

Dorajoo

et al. 2015

Atherosclerosis

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Objective Paraoxonase 1 (PON1) plays an important role in reducing the risk of coronary heart disease (CHD). Smoking is known to reduce PON1 activity. We aimed to investigate the effects of interactions between PON1 variants and smoking on CHD in the Singaporean Chinese population. Methods In a case-control study nested within Singapore Chinese Health Study (N = 1914), subjects with and without CHD were classified into never-smokers and ever-smokers (ever smoked at least one cigarette a day for 1 year or longer). Associations at four independent SNPs at the PON1 locus (rs3735590, rs3917550, rs662, rs3917481) with CHD were evaluated using logistic regression, before/after stratification on smoking status. Interactions between smoking and PON1 variants were analyzed with likelihood ratio tests, by including the SNP*smoking interaction term in regression analyses. Results The T allele at the coding SNP, rs662, was associated with higher risk of CHD in ever-smokers only (OR = 1.35, 95% CI 1.08–1.68; adjusted P = 0.036). At the miR-SNP, rs3735590, carrying at least one copy of minor allele T was associated with increased risk of CHD in a dominant manner in never-smokers only (OR = 1.53, 95% CI 1.11–2.11; adjusted P = 0.036). Significant interactions between two PON1 SNPs and smoking in relation to CHD risk were identified (adjusted P = 0.012 for rs662; adjusted P = 0.044 for rs3735590). These associations remained significant after adjustment for known CHD risk factors and upon correction for multiple tests. Conclusions Two PON1 SNPs, rs662 and rs3735590, were found to significantly interact with cigarette smoking to modulate the risk of CHD in the Singaporean Chinese population.

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Paraoxonase 1 gene polymorphisms contribute to coronary artery disease risk among north Indians

Cited by 33 publications

References 39 publications

Paraoxonase 1 Gene Polymorphisms (Q192R and L55M) Are Associated with Coronary Artery Disease Susceptibility in Asian Indians

Paraoxonase 1 Gene Polymorphisms (Q192R and L55M) Are Associated with Coronary Artery Disease Susceptibility in Asian Indians

Paraoxonase-1 55 LL Genotype Is Associated with No ST-Elevation Myocardial Infarction and with High Levels of Myoglobin

Interaction effects between Paraoxonase 1 variants and cigarette smoking on risk of coronary heart disease in a Singaporean Chinese population

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