GENETIC-POLYMORPHISM OF PARAOXONASE AND THE RISK OF CORONARY HEART-DISEASE

Recent studies have implicated paraoxonase, an HDL-associated enzyme, in providing protection against LDL oxidation, thus affecting the risk of coronary heart disease (CHD) in the general population. In this st udy, we evaluated the distribution of a biallelic PON polymorphism at codon 192 (A and B alleles) and its relationship with plasma lipids an d CHD in two racial groups comprising Asian Indians and Chinese from S ingapore. The frequency of the B allele was significantly high er in C hinese control subjects than in Indian control subjects (0.58 versus 0 .33; P<.0001). With the exception of a marginal effect on apolipoprote in A-I levels in Indians, no other significant association was observe d between the PON polymorphism and quantitative lipid traits in either racial group. However, there was a race-specific association of the B allele with CHD in Indians but not in Chinese. The Indian CHD patient s had a significantly higher frequency of the B allele than control su bjects (.43 versus .33; P=.014). The age- and sex-adjusted odds ratio for developing CHD with the B allele (BB+AB genotypes) was 2.01 (95% C I, 1.17 to 3.45; P=.011) compared with the A allele (AA genotype). Whe n the Indian patients were stratified into subgroups, the association remained significant in nondiabetic patients (odds ratio, 2.29; P=.008 ), and it became stronger in patients with myocardial infarction (odds ratio, 2.94; P=.004) than in patients without myocardial infarction ( odds ratio, 1.11; P=.76). These data indicate that a common polymorphi sm in the PON gene is an independent risk factor for CHD in population s with white ancestry.