Dataset Information

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

ABSTRACT:

Objective

TCF7L2 is a repressor and transactivator of genes, and its variants are strongly associated with diabetes. This study aimed 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.

Methods

Single nucleotide variants (SNVs) have been genotyped using the TaqMan allelic discrimination assays in 2,024 (51.3% in women, age: 55±11.8) Turkish adults participating in the TARF study. Statistical analyses were used to investigate the association of genotypes with clinical and biochemical measurements.

Results

Among the TARF study participants, 11.7%, 24.3%, 14.1%, and 38.3% had diabetes, hypertension, coronary heart disease (CHD), and obesity, respectively. 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). Also, both SNVs and the diplotypes of common haplotype (H1) remained strongly associated with type 2 diabetes after risk factors were adjusted (p<0.05).

Conclusion

T allele homozygosity of two SNVs as well as the diplotype H1-/H1- reflects risk of diabetes primarily in men. Enhanced CHD risk is determined by the presence of diplotype H1-/H1- among nondiabetic participants.

SUBMITTER: Yuzbasıogulları AB

PROVIDER: S-EPMC7724383 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPrevious studies reported increased risk of cardiac events in subjects with fasting blood glucose (FBG) levels lower than the diagnostic threshold of diabetes mellitus. However, whether increased cardiac events in those with upper normal FBG is secondary to the shift of their cardiac sympathovagal balance towards sympathetic predominance is unknown.AimsTo assess the association between FBG levels and cardiac autonomic modulation (CAM) in euglycaemic healthy subjects based on heart rate variability (HRV) derived indices.Subjects and methodsThe study enrolled 42 healthy young adults. Following sociodemographic and clinical assessment, blood samples were collected to measure FBG levels. Five minutes ECG recordings were performed to all participants to obtain frequency domain HRV measurements, namely the natural logarithm (Ln) of total power (LnTP), very low frequency (LnVLF), low frequency (LnLF) and high frequency (LnHF), low frequency/ high frequency ratio (LnLF/HF), normalized low frequency (LF Norm) and high frequency (HF Norm).ResultsFBG levels correlated positively with LnHF (r = 0.33, P = 0.031) and HF Norm (r = 0.35, P = 0.025) and negatively with LF Norm (r = -0.35, P = 0.025) and LnLF/HF (r = -0.33, P = 0.035). LnHF and HF Norm were significantly decreased in subjects with the lower (4.00 (1.34) ms2/Hz and 33.12 (11.94) n.u) compared to those with the upper FBG quartile (5.64 (1.63) ms2/Hz and 49.43 (17.73) n.u, P = 0.013 and 0.032 respectively). LF Norm and LnLF/HF were significantly increased in subjects with the lower (66.88 (11.94) n.u and 0.73 (0.53)) compared to those with the higher FBG quartile (50.58 (17.83) n.u and 0.03 (0.79), P = 0.032 and 0.038 respectively).ConclusionThe present study is the first to demonstrate that rise of blood glucose concentration, within physiological range, is associated with higher parasympathetic, but lower sympathetic CAM. Further researches are needed to set out the glycemic threshold beyond which further increase in glucose level readjusts sympathovagal balance towards sympathetic predominance again.