Paraoxonase 1 gene polymorphisms contribute to coronary artery disease risk among north Indians.
BACKGROUND
Polymorphisms in paraoxonase 1 (PON1) coding for PON1 enzyme have been studied as genetic markers of coronary artery disease (CAD). PON1 Q192R and PON1 L55M polymorphisms have been analyzed extensively, but data on association and role of these polymorphisms in the etiology of CAD are conflicting. In this study, we tested the genetic association between PON1 Q192R and PON1 L55M polymorphisms and CAD among north Indians.


METHODS
Two hundred eighty-five angiographically proven patients with coronary artery disease and 200 sex-matched and ethnically matched controls were genotyped for 2 PON1 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Genotype/ allele frequencies were compared in patients and controls using the chi-square test.


RESULTS
At PON1-192 locus, there were significant differences between patients and controls (P< 0.05), leading to significant odds ratios for RR genotype (OR= 1.92, CI: 1.19-3.10) and *R allele (OR= 1.30, CI: 1.00-1.70). These odds ratios were higher in the sub-sample of smokers (2.84 and 1.45, respectively). Binary logistic regression analysis also confirmed that *R allele carriers (QR and RR) have a higher risk of CAD (OR= 3.54, CI: 1.67-5.53). PON1-55 locus did not show significant differences between patients and controls, but LL genotype and *L allele were significant risk factors in the nonsmoker group. RL haplotype was also significantly associated with CAD risk (OR= 1.44, CI: 1.08-1.93).


CONCLUSIONS
PON1-192R allele and RR genotype are significantly associated with CAD patients from the north Indian population (Uttar Pradesh). This association was stronger in smokers, supporting the conclusion that an interaction between PON1 activity and smoking augments CAD risk. Further studies with larger sample size are warranted to confirm these associations in different Indian populations.
Agrawal
S
S
Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Tripathi
Gaurav
G
Prajnya
R
R
Sinha
Nakul
N
Gilmour
A
A
Bush
L
L
Mastana
S
S
D043303:Aryldialkylphosphatase / Q000235:genetics*; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007194:India; D016015:Logistic Models; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012306:Risk
D043303:Aryldialkylphosphatase