The APOE -219G/T and +113G/C polymorphisms affect insulin resistance among Turks.
The -219G/T (rs405509) and +113G/C (rs440446) polymorphisms within the regulatory region of the apolipoprotein E (APOE) gene have been related to the transcriptional activity of the gene. We examined the effect of the stated polymorphisms and their construct haplotypes with the APOE ɛ2/ɛ3/ɛ4 polymorphism on lipid levels and insulin resistance in the Turkish Adult Risk Factor Study. Randomly selected 1774 adults (mean age, 55.0 ± 11.7 years; 51.2% women) participating in the population-based Turkish Adult Risk Factor Study were cross-sectionally analyzed for the -219G/T, +113G/C, and ɛ2/ɛ3/ɛ4 polymorphisms as well as their haplotypes. Insulin resistance was defined as the 70th percentile in the sample (>2.51) of the homeostatic model assessment (HOMA). The frequencies of the -219T and +113C alleles were 0.477 and 0.423, respectively; and those of haplotype 1 (GGɛ3) and haplotype 2 (TCɛ3) were 44.1% and 41.9%, respectively. The -219G/T and +113G/C genotypes (both P < .04) and diplotypes of haplotype 2 (TCɛ3) (P < .014) were inversely related to serum fasting insulin and the HOMA index, even after controlling for 8 relevant covariates, but not to serum lipids. Within the APOE3 group, haplotype 2 (TC-/TC+) heterozygotes had an odds ratio of 0.66 (95% confidence interval, 0.42-0.99) for HOMA of insulin resistance after adjusting for 8 covariates. APOE promoter polymorphisms and their diplotypes are independently related with serum fasting insulin levels and HOMA index among Turks.
Komurcu-Bayrak
Evrim
E
Department of Genetics, Institute for Experimental Medicine, Istanbul University, 34080, Istanbul, Turkey. evrimbayrak@yahoo.com
Onat
Altan
A
Yuzbasiogullari
Berna
B
Mononen
Nina
N
Laaksonen
Reijo
R
Kähönen
Mika
M
Hergenc
Gulay
G
Lehtimäki
Terho
T
Erginel-Unaltuna
Nihan
N
D000328:Adult; D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014421:Turkey / Q000453:epidemiology
D001057:Apolipoproteins E; D007328:Insulin; D008055:Lipids