ROLE OF THE APOB GENE POLYMORPHISM (c.12669G>A, p.Gln4154Lys) IN CORONARY ARTERY DISEASE IN THE INDIAN PUNJABI POPULATION
Sharma R1,*, Mahajan M2, Singh B1, Singh G3, Singh P3
*Corresponding Author: Ritu Sharma, Department of Biochemistry, Government Medical College, Circular Road, Amritsar-143001, Punjab, India; Tel.: +91-183-257-3637; Fax: +91-183-242-6506: E-mail: ritu_gmc@ rediffmail.com
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DISCUSSION

In the present study, the role of the APOB gene polymorphism (c.12669G>A,p.Gln4154Lys) was studied in native Indian Punjabi subjects suffering from CAD. Three APOB genotypes, i.e., R+R+, R+R– and R–R– are possible. However, only two genotypes R+R+ and R+R– were observed in both control subjects and CAD patients in this study. The R–R– genotype was not observed. The occurrence of this genotype in other populations has been reported to vary from infrequent to nil [23]. Frequency of the R– allele was observed to be high in CAD patients when compared to control subjects in the population under study. In other populations, increased frequency of the R– allele has also been reported in CAD patients as compared to normal subjects [8,9]. On the other hand, no significant difference in the frequency of the R– allele has been reported in South Asian CAD patients and normal subjects living in Britain [10]. Similar results have been reported in the Brazilian population [11]. Thus, the R– allele is not associated with CAD in all the populations. In the Indian Punjabi population, the R+R– genotype was more frequent in CAD patients in comparison to control subjects and accordingly, the frequency of the R– allele was higher in CAD patients. This clearly indicates that the R– allele is associated with increased susceptibility toward CAD development in our population. In a study on the South Indian Tamil population, the frequency of the R– allele has been reported to be 0.054 [13], which is close to that observed in our population (0.04). It may be noticed that this comparison was done in a healthy population only and it may be possible that frequency of the R– allele would be more in the Tamil population suffering from CAD. However, they have not reported this data. No significant variations in lipid and lipoprotein cholesterol levels in CAD patients having either the R+R+ or R+R– genotype were observed. Similar results have been reported in South Indian [13] and in Brazilian populations [11]. Hegele et al. [8] also observed no difference in total or LDL cholesterol levels in CAD patients and normal subjects with different apoB genotypes in the American population. However, positive association of APOB gene EcoR1 polymorphism with elevated lipid levels has been reported in the Russian population [12]. In the present study, we observed raised serum apoB levels in CAD patients with the R+R– genotype as compared to those having the R+R+ genotype. On the contrary, insignificant difference in apoB levels of CAD patients with different apoB genotypes has been reported in the American population. In the Indian population from the city of Lucknow, Uttar Pradesh, India, higher levels of apoB and LDL cholesterol were reported in CAD patients with the R+R+ apoB genotype [24]. Thus, the relationship between the R– allele of apoB and raised serum apoB levels is not consistent in all populations and thus need to be verified in different ethnic groups. Raised serum apoB levels were associated with the R– allele in our population. It seemed interesting to investigate if this APOB gene polymorphism could affect the heterogeneity of LDL particles and its oxidation. However, no significant difference was observed in MDA-LDL levels and apoB carbonyl content in CAD patients having the R+R+ and R+R– genotypes, thereby indicating that this APOB gene polymorphism does not affect the LDL oxidation status in the Indian Punjabi population. Independent of the genotype, both MDA-LDL levels and apoB carbonyl content were raised in CAD patients in comparison to control subjects. Similar results were observed when Log triglyceride/ HDL-C values were compared in CAD patients having the R+R+ or R+R– APOB genotypes. An increased susceptibility of LDL to oxidation has been reported in CAD patients by other investigators [25,26]. Overall, CAD patients had increased predominance of small dense LDL particles that are more prone to oxidation. However, this observation was independent of APOB genotype. This clearly indicates that some other factors such as environment or nutrition might be more potent in bringing structural and functional changes in apoB of LDL.



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