Paraoxonase 1 glutamine / arginine 192 polymorphisms in three ethnic groups in Malaysia

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Date
2009-02
Authors
Haji Abdul Hana, Normaizam
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Abstract
Coronary Heart Disease (CHD) is the major cause of death globally, including in Malaysia. Despite of sharing almost similar environmental exposure, the prevalence of CHD was highest in Indian population compared to the Malays and Chinese. We hypothesized that the Indians have genetic predisposition to CHD. Paraoxonase 1 (PON 1) glutamine (Q) I arginine (R) 192 polymorphism has been shown to be associated with CHD. This study was aimed to determine the distribution of lipid profile and genotype among the three ethnic groups (Malays, Chinese and Indians) and also to study the relationship of lipid profile and PON 1 genotype. A total of 155 healthy blood samples were collected (54 Malays, 50 Chinese and 51 Indians) for lipid profile estimation and PON 1 genotyping. The genotyping procedures involved the DNA extraction, PCR amplification, Alw 1 digestion and agarose gel electrophoresis. Statistical data were analyzed by ANOVA, ANCOVA, Chi square and Pearson correlation tests. The mean concentrations of plasma total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and TC:HDL-C ratio were significantly higher in Malays and Chinese than Indians (TC: p=O.035; LDL-C: p=0.039; p=O.016). However, there were no significant differences in the plasma triglycerides (TG) and high density lipoprotein-cholesterol (HDL-C) concentrations (TG: p=O.610; HDL-C: p=O.225). The overall genotype compositions were 34 % of QQ, 20 % of QR and 46 % of RR. The allele frequencies were 0.442 and 0.558 for Q and R respectively for total subjects. The frequencies of QQ, QR and RR genotypes were 39 %, 18 % and 43 % for both Malays and Indians groups and 24 %, 24 % and 52 % for Chinese group respectively. The allele frequencies were 0.48 and 0.52 for Q and R allele respectively for both Malays and Indians, while it was 0.36 for Q and 0.64 for R in Chinese. PON 1 genotype (p=0.483) and allele distributions (p=O.134) were statistically not significant among the ethnic groups. After classification by NCEP-ATP III guidelines, the frequency of lower HDL group were 2.2 times and 3.2 times more in Indians compared to Malays and Chinese respectively. The mean concentrations of plasma TC, LDL-C and TC:HDL-C ratio were significantly higher in RR compared to QR and QQ (TC: p=O.013; LDL-C: p=0.019; TC:HDL-C: p=O.03). The plasma HDL-C was also significantly different but it was higher in QR than RR and QQ (p=0.002). However, there was no significant difference in the plasma TG among three genotypes (p=0.292). As a conclusion, the highest CHD prevalence in Indian population in Malaysia may be due to the more frequency of subjects with lower HDL-C group. The distribution of PON 1 glutamine I arginine polymorphism is independent of ethnicity. The PON 1 R allele was associated to elevation of 11.1 % of TC, 16.5 % of LDL-C and 16.3 % of TC:HDL-C ratio. PON 1 Gin I Arg 192 polymorphism should be added as one of the risk factors for determination of the progression of premature CHD among healthy populations of Malaysia
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Coronary Heart Disease is the major cause , of death globally including in Malaysia.
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