Genetic variants of APOE and CCR4 as determinants of myocardial infarction among type 2 diabetes patients: a South Indian case-control analysis.

BACKGROUND

Myocardial infarction (MI) is a leading cause of mortality worldwide, and Type 2 Diabetes Mellitus (T2DM) markedly increases cardiovascular risk. Genetic variation in lipid metabolism pathways, such as APOE, and in immune regulatory genes, such as CCR4, may contribute to myocardial infarction susceptibility among individuals with T2DM.

OBJECTIVE

This study aimed to evaluate the individual and combined effects of APOE (rs429358 and rs7412) and CCR4 (rs2228428) polymorphisms on MI risk in a South Indian population.

METHODS

In this prospective case–control study, 400 participants were enrolled and categorized into four groups: controls (n = 100), MI (n = 100), T2DM (n = 100), and MI + T2DM (n = 100). Genotyping was performed using ARMS-PCR and Sanger sequencing. A genetic risk score (GRS) ranging from 0 to 2 was generated using the APOE ε4 allele and the CCR4 TT genotype. Associations were evaluated using odds ratios and logistic regression analysis.

RESULTS

The APOE ε4 allele showed a strong association with disease in all affected groups, with the highest risk observed in MI + T2DM subjects (OR = 8.2). The CCR4 TT genotype was significantly associated with MI + T2DM (OR = 22.97) but not with isolated T2DM. The combined GRS demonstrated a clear dose–risk effect, with individuals carrying both high-risk variants showing the most significant susceptibility to MI in the presence of T2DM (OR = 19.60).

CONCLUSION

Our findings indicate a synergistic interaction between APOE and CCR4 variants, particularly in individuals with T2DM, suggesting clinical value for genetically-based risk stratification in South Indian populations.