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Sex-specific associations of TCF7L2 variants with fasting glucose, type 2 diabetes and coronary heart disease among Turkish adults [Anatol J Cardiol]
Anatol J Cardiol. Ahead of Print: AJC-57736 | DOI: 10.14744/AnatolJCardiol.2020.57736  

Sex-specific associations of TCF7L2 variants with fasting glucose, type 2 diabetes and coronary heart disease among Turkish adults

Ayse Berna Yuzbasiogullari1, Evrim Komurcu-Bayrak1, Altan Onat2, Gunay Can3, Nina Mononen4, Reijo Laaksonen4, Mika Kähönen5, Terho Lehtimäki4, Nihan Erginel-Unaltuna1
1Department of Genetics, Aziz Sancar Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey
2Emeritus Professor, Department of Cardiology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
3Department of Public Health, Cerrahpaža Medical Faculty, Istanbul University Cerrahpasa, Istanbul, Turkey.
4Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
5Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland

Objective: TCF7L2 is a repressor and transactivator of genes and its variants are strongly associated with diabetes. Our aim was to evaluate the sex-specific relationship between the most common TCF7L2 gene variants (-98368G>T, rs12255372 and -47833C>T, rs7903146) with diabetes and coronary heart disease in Turkish Adult Risk Factor (TARF) Study.
Research Design and Methods: We genotyped single nucleotide variants (SNVs) using the Taqman allelic discrimination assays in 2024 (% 51.3 women, age: 55±11.8) Turkish adults participating in TARF study. Statistical analyses were used to investigate the association of genotypes with clinical and biochemical measurements.
Results:
11.7% of the TARF study participants had diabetes, 24.3% had hypertension, 14.1% had coronary heart disease (CHD), and had 38.3% obesity. The frequencies of T allele for -47833C>T and -98368G>T in Turkish adults were determined to be 0.35 and 0.33, respectively. -47833C>T was significantly associated with higher fasting glucose concentrations in all participants, especially in men. Both SNVs were significantly associated with diabetes and CHD in all participants (p<0.05). When study population was stratified according to sex, -98368G>T was associated with diabetes in women (p=0.041) and -47833C>T was associated with diabetes and CHD in men (p=0.018 and p=0.032, respectively). And also, the strong association of type-2 diabetes with both SNVs and the diplotypes of common haplotype (H1) remained after adjustment for risk factors (p<0.05).
Conclusions: T allele homozygosity of two SNVs as well as the diplotype H1-/H1- reflects risk of diabetes primarily in men. Enhanced CHD risk is provided by the diplotype H1-/H1- in nondiabetic participants.

Keywords: TCF7L2, variants, type 2 diabetes, coronary heart disease, TARF study.




Corresponding Author: Nihan Erginel-Unaltuna, Türkiye


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