The aim of this study was to determine combined effect of Apolipoprotein AI(-75G/A) and AIV(T347S) gene polymorphisms and its role in coronary artery disease(CAD).Background
A common polymorphism of aguanine (G) to adenine (A) substitution (G/A) at 75 bp(M1-) in the promoter region of the apoA1 gene has traditionally been associated with a significantly higher Lp(a) and HDL-c levels by numerous workers. A Thr347Ser polymorphism in exon 3 of Apo AIV gene has also been significantly associated with LDL-c and TG concentrations by many, but their combined effect in pathogenesis of CAD has seldom been investigated.Methods
This was prospective study; the subjects were included from a tertiary care centre in Uttar Pradesh, the most populated province situated in northern India. The study population comprised of consecutive 200 proven CAD patients and 200 disease free controls. Genotyping technique used was polymerase chain reaction(PCR) followed by restriction fragment length polymorphism(RFLP).Results
Baseline characteristics and risk factor distribution including incidence of diabetes, hypertension, smoking, family history of CAD along with mean levels of various lipid parameters were found to be significantly higher in patients than in controls (p < 0.001). No significant association with CAD was detected when the various genotypes/allele frequencies arising due to Apo AI(-75G/A) and AIV(T347S) gene polymorphisms were compared individually(p > 0.05). However when these two polymorphisms were clubbed together, we found significantly higher relative risk for CAD in patients carrying mutant alleles (Odds ratio = 1.33,p = 0.03) for both the polymorphisms. Other genotypic combinations did not reveal any significant association with the disease.Conclusion
The results of our study indicate that apoAI(-75 G/A) and AIV(T347S) polymorphisms does not only affect the lipid levels of an individual (as reported in numerous studies all around the world) but also contribute in increasing the risk of CAD. The complex gene-gene interaction between the two studied genes could have resulted in an increased relative risk in patients carrying mutant combinations.