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Diabetes and Vascular Disease Research
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The ApoAI-CIII-AIV gene cluster and its relation to lipid levels in type 2 diabetes mellitus and coronary heart disease: determination of a novel susceptible haplotype

Puneetpal Singh

Molecular Genetics Laboratory, Department of Human Biology, Punjabi University, Patiala-147002, Punjab, India.

Monica Singh

Molecular Genetics Laboratory, Department of Human Biology, Punjabi University, Patiala-147002, Punjab, India.

Sunil Gaur

Sai Cardio Clinic, Khanna, Punjab, India.

Taranpal Kaur

Diabetes Division, City Medsave Hospital, Ferozepur, Punjab, India.

The present study investigated genetic variation in the 3’ flanking region of ApoA-I (PstI), the 3’ untranslated region of ApoC-III (SstI) and intron 2 of ApoA-IV (XbaI) in 435 type 2 diabetes mellitus patients, divided according to the presence or absence of coronary heart disease (CHD). Uncommon allele frequencies (P2, S2, X2) were 17.5%, 32.5%, 16.2% and 29.5%, 17.9%, 13.8% in patients with and without CHD, respectively. Linkage disequilibrium (D’ = 0.31-0.73, p<0.01) was observed in all diallelic pairs except XbaI/PstI and XbaI/SstI in patients having CHD. Haplotype analysis revealed that P1-S2-X1 is a susceptibility haplotype that increases the risk of CHD in diabetes (OR 2.85, CI 1.51-5.61), exacerbating risk (OR 3.57, CI 1.81-7.45) even after adjustment for confounders.

The findings in the present study suggest that each unit of P1-S2-X1 in diabetes increases the risk of CHD by a factor of 1.37+0.307 (β ± SE), which is manifest in its multiplicative mode.

Key Words: coronary heart disease • type 2 diabetes • Punjab • ApoA-I gene • ApoC-III gene • ApoA-IV gene • haplotypes • linkage disequilibrium

Diabetes and Vascular Disease Research, Vol. 4, No. 2, 124-129 (2007)
DOI: 10.3132/dvdr.2007.030
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