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.
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 (beta + SE), which is manifest in its multiplicative mode.
Singh
Puneetpal
P
Molecular Genetics Laboratory, Department of Human Biology, Punjabi University, Patiala-147002, Punjab, India. singh.puneet@rediffmail.com
Singh
Monica
M
Gaur
Sunil
S
Kaur
Taranpal
T
D024509:3' Flanking Region; D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000235:genetics*; D053305:Apolipoprotein C-III / Q000235:genetics*; D001054:Apolipoproteins A / Q000235:genetics*; D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007194:India; D007438:Introns; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length; D018570:Risk Assessment; D012307:Risk Factors
D020413:3' Untranslated Regions; D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D008055:Lipids; C022205:apolipoprotein A-IV