Premium
DGAT1 promoter polymorphism associated with alterations in body mass index, high density lipoprotein levels and blood pressure in Turkish women
Author(s) -
Ludwig EH,
Mahley RW,
Palaoglu E,
Özbayrakçı S,
Balestra ME,
Borecki IB,
Innerarity TL,
Farese RV
Publication year - 2002
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1034/j.1399-0004.2002.620109.x
Subject(s) - endocrinology , medicine , body mass index , allele , biology , blood pressure , turkish population , genetics , genotype , gene
Triglyceride synthesis is catalyzed by acyl CoA:diacylglycerol acyltransferases (DGAT), microsomal enzymes that use diacylglycerol and fatty acyl CoAs as substrates. Because DGAT1 expression is up‐regulated during adipocyte differentiation and DGAT1 deficiency is associated with leanness in mice, we hypothesized that alterations in DGAT1 expression may affect human body weight. We identified five polymorphisms in the human DGAT1 promoter and 5′ non‐coding sequence in a random Turkish population. Functional analysis of one common variant, C79T, revealed reduced promoter activity for the 79T allele in cultured cell lines. In 476 Turkish women, the 79T allele was associated with lower body mass index (BMI) (p = 0.004), conferring an odds ratio of 2.0 (95% CI = 1.30–3.07, p = 0.0001) for BMI ≤ 20. Interestingly, after controlling for the influence of BMI, the 79T allele was also associated with higher plasma HDL cholesterol levels (p = 0.0006) and lower diastolic blood pressure (p = 0.019) in these women. No association was found in Turkish men ( n = 846). Our findings suggest that genetic variation at the DGAT1 locus may influence BMI and other metabolic parameters associated with cardiovascular risk in selected human populations.