The GLN-Arg192 Polymorphism of Human Paraoxonase 1 Gene and the Associated Phenotype Variation Is Associated With Coronary Artery Disease in South-Indian Patients

Abstract

BACKGROUND Paraoxonase 1, an arylesterase, is associated with high-density lipoprotein and it prevents LDL from peroxidation by hydrolysing lipid peroxides and thereby providing protection against atherosclerosis. A polymorphism of paraoxonase 1 gene provoking a glutamine-to-arginine (A-allele or Q allele to B-allele or R allele) interchange at aminoacid-192 has been reported to determine differences in arylesterase activity towards LDL's oxidised aryl esters, hydrolysed at a higher rate by Q-alloenzyme than Ralloenzyme. AIM We carried out this study to determine the association of paraoxonase 1 gene Q192R polymorphism (R-allele) with coronary atherosclerosis and to find out if the low arylesterase activity caused by the paraoxonase 1 gene Q192R polymorphism (Rallele) is associated with atherosclerosis. STUDY DESIGN Case control study. METHODS Genotype analysis was done on 181 angiographically proven coronary atherosclerosis patients and 177 healthy controls by polymerase chain reaction followed by restriction digestion. Paraoxonase 1 arylesterase activity was estimated with phenyl acetate as substrate. RESULTS Cases had significantly higher frequency of R+ genotype (RR and QR) than control subjects (0.78 versus 0.49; P=.001). Significantly, lower plasma paraoxonase 1 activity was observed in coronary atherosclerosis patients as compared to healthy controls (71.3 kIU/mL versus 84.74 kIU/mL, P <0.05). Risk stratification is possible based on paraoxonase 1 activity-<65 kIU/mL-high risk, 65-80 kIU/mL = moderate risk, >80 kIU/mL-low risk for atherosclerosis. The mean paraoxonase 1 activity among R+ genotypic individuals is 63.52 kIU/mL whereas the mean paraoxonase 1 activity among R-genotype is 103.26, p value is 0.004. On univariate analysis, the odds ratio for R+ genotype is 3.6 (p=0.00). On multivariate analysis, the odds ratio for R+ genotype is 2.5 (p=0.00). CONCLUSION The low plasma Paraoxonase 1 activity and the R genotype maybe independent risk factors for coronary atherosclerosis.

Role of Paraoxonase-1 (Q192R) Gene Polymorphism in Coronary Artery Disease in Saudi Arabian Population

“…Whereas interestingly, the odds ratio of developing CAD were increased close to 2.706 -fold in the RR genotypes compared to healthy controls in Saudi populations. Our results were similar with recent findings of Saudi Arabian, North African and South Indian studies which also reported that CAD with RR genotype has more than 2 to 3 fold risk of developing coronary arthrosclerosis 10,17,26 .…”

“…The results of the Caerphilly study, the first potential epidemiological study of PON1 and CAD, also showed that activity of serum PON1 anticipate the coronary proceedings independent of all other coronary threat factors, as well as HDL 25 . Moreover, a recent study from Chandrasekaran S 2016 26 and Tan Y et al 27 supports the theory that lesser PON1 activity in the development of atherosclerosis. In contrast, in an Iranian 28 and Indian case-control studies 29 showed that no differences occur in PON1 activity in CAD patients and healthy individuals.…”

“…It is very clear that there are different reports by sharing of alleles which was consider to their greater or lesser allele in different ethnic populations. Numerous studies revealed that there is a vast relationship between the PON1 192 R (Arg) allele in the progress of CAD 36,26 . Zama T et al 37 from Japan described that, the occurrence of PON 1 192 R allele was notably related with CAD possibility even though controlling for a risk factor.…”

“…There was a noteworthy low PON1 activity among in RR genotypic individuals (68.5±11.5) when compared to QR (75.8±10.8) and QQ (86.3±11.0) genotypes (p<0.002). The possible mechanism for replacement of glutamine by arginine in 192 nd position reduces the affinity of N-terminal amphipathic helix of PON enzyme with HDL thereby the enzyme gets destabilized and the activity is lowered 26 . Finally, we carried out multiple linear regression analysis of PON1 gene polymorphism and the confounding variables.…”

Paraoxinase-1 Activity in Patients with Subclinical Hypothyroidism: A link to Atherosclerosis

“…Recently, dysfunctional, or proinfl ammatory HDL was indicated as a pro-atherogenic factor. Th e protective function of HDL against atherogenesis could be partly explained by its main constituent, PON1 [7].…”