Role of the APOB Gene Polymorphism (c.12669G>A, p. Gln4154Lys) in Coronary Artery Disease in the Indian Punjabi Population

Abstract

High concentration of apolipoprotein B (apoB) is a risk factor for coronary artery disease (CAD). The association of the APOB gene polymorphism c.12669G>A, p.Gln4154Lys with the risk of CAD varies considerably in different populations. The present study represents the first investigation regarding the role of this APOB gene polymorphism with CAD in the Indian Punjabi population. We have studied the APOB gene polymorphism c.12669G>A, p.Gln4154Lys and its relationship with lipid, apoB, low-density lipoprotein (LDL) heterogeneity and oxidation in subjects suffering from CAD. The study was conducted on 87 patients with CAD; 75 healthy subjects served as controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the DNA polymorphism in the APOB gene. Frequency of R− (mutant) allele was significantly high (p <0.05) in CAD patients when compared to controls. Variations in serum lipid levels in the R+R+ and R+R− APOB genotypes were insignificant (p >0.05). However, serum apoB levels were significantly raised (p <0.05) in CAD patients with the R+R− genotype as compared to those with the R+R+ APOB genotype. Coronary artery disease patients had raised significantly raised (p <0.01) Log triglyceride/high density lipoprotein-cholesterol (HDL-C) ratio, apoB carbonyl content and increased malondialdehyde-low density lipoprotein (MDA-LDL levels, irrespective of APOB genotype as compared to controls. Carriers of the R− allele are at higher risk of CAD, probably because of elevated serum apoB levels in the Indian Punjabi population. Overall, it may be concluded that the R− allele might be associated with increased susceptibility towards CAD development in the Indian Punjabi population, and one of the linking factor is the elevation in serum apoB levels. However, this association needs further evaluation in a larger population. Secondly, the robust mechanism behind the positive association of the R− allele with raised serum apoB levels needs to be explored, which might be helpful in the strengthening the observed results.

Study on Association of APOB Gene Polymorphism with Glycation of Low Density Lipoproteinin Type 2 Diabetes

“…R + allele was found to be more common in our population. Similar results were reported from Punjab and Tamil Nadu also [8,22]. There was no statistically significant difference in the LDL-C or any other lipid parameters among different genotypes of APOB in our study population.…”

“…Gene polymorphism may have its consequences ranging from effect on structure function relationship of a protein or alteration in protein expression level. Role of the APOB gene polymorphism in coronary artery disease in the Indian Punjabi population has been evaluated by Sharma et al [8]. Thus we designed this study to evaluate the effect of APOB gene polymorphism on levels of Apo B containing lipoproteins and their glycation.…”

“…Apo B-100 is ligand for LDL-receptor-mediated endocytosis of LDL particles. Raised serum ApoB levels are associated with increased risk of coronary artery disease (CAD) [5,6] and several APOB polymorphisms have been evaluated for their association with lipid levels and CAD in different populations [7][8][9][10]. One such polymorphism in the 29th exon (c.12669 G>A) results in Glu4154Lys amino acid substitution.…”

Association of the 12669G>A Apolipoprotein B Gene Polymorphism with Apo-B Serum Level and Lipid Profile in Patients with Coronary Artery Disease Comparing with Individuals Without Coronary Artery Disease in Zanjan Population of Iran

“…Similar results have been reported in the Brazilian population [18,24], Marshal et al [25] and also in South Asian subjects living in Britain [17]. On the other hand, remarkable positive connections in the frequency of the R-allele and CAD has been reported in other population [15,16,26,27]. Being incompatible with other studies, in our population Apo B serum levels was remarkably higher in individuals with the R?Rgenotype.…”

A novel method for whole blood PCR without pretreatment

“…480 bp fragment is known to have a restriction site for EcoR1, which is lost if there is single base pair mutation from guanidine to adenosine at c.12669G>A, P.Gln4154Lys at exon29 (Shoulders et al, 1985). This mutation is linked with the risk of coronary artery disease in several populations and in our previous studies the polymorphism in APOB gene and its relationship with coronary artery disease was studied in Indian Punjabi population (Sharma et al, 2011).…”