👤 Ilknur Coban

Coronary artery disease (CAD) is the leading cause of death worldwide despite advanced treatment and diagnosis strategies. Angiopoietin-like protein 8 (ANGPTL8) mainly functions in the lipid mechanism, which is a dysregulated mechanism during CAD pathogenesis. In this study, we aimed to determine the associations between an ANGPTL8 polymorphism rs2278426 and the severity, presence, and risk factors of CAD. A total of 1367 unrelated Turkish individuals who underwent coronary angiography were recruited for the study and grouped as CAD (n = 736, ≥50 stenosis) and non-CAD (n = 549, ≤30 stenosis). Also, subjects were further divided into groups regarding type 2 diabetes mellitus (T2DM) status. Subjects were genotyped for rs2278426 (C/T) by quantitative real-time PCR. Secondary structure analyses of protein interactions were revealed using I-TASSER and PyMOL. Among CAD patients, T allele carriage frequency was lower in the T2DM group (p = 0.046). Moreover, in male non-CAD group, T allele carriage was more prevalent among T2DM patients than non-T2DM (p = 0.033). In logistic regression analysis adjusted for obesity, T allele carrier males had an increased risk for T2DM in non-CAD group (OR = 2.244, 95 % CI: 1.057-4.761, p = 0.035). Also, in T2DM group, stenosis (p = 0.002) and SYNTAX score (p = 0.040) were lower in T allele carrier males than in non-carriers. Analyzes of secondary structure showed that ANGPTL8 could not directly form complexes with ANGPTL3 or ANGPTL4. In conclusion, T allele carriage of ANGPTL8 rs2278426 has a protective effect on CAD in T2DM patients. Further research should be conducted to explore the association between ANGPTL8 polymorphism (rs2778426) and CAD. Show less

Norepinephrine (NE) is a well-known appetite regulator, and the nor/adrenergic system is targeted by several anti-obesity drugs. To better understand the circuitry underlying adrenergic appetite control, here we investigated the paraventricular hypothalamic nucleus (PVN), a key brain region that integrates energy signals and receives dense nor/adrenergic input, using a mouse model. We found that PVN NE level increases with signals of energy deficit and decreases with food access. This pattern is recapitulated by the innervating catecholaminergic axon terminals originating from NTS Show less

The aim of this study was to examine the relationship between APOA4 gene T347S polymorphism with obesity measures and serum lipids in Turkish adults. Randomly selected sample of 1,554 adults (754 men, mean age 50.4 ± 11.9 years and 800 women, mean age 49.6 ± 11.8 years) were included in the study. 346 Women (43.2 %) were postmenopausal. Genotyping was performed by using hybridization probes in real-time PCR. Not men but postmenopausal women, carrying the S347 allele, were associated with 1.5 kg/m(2) higher BMI (P = 0.016) and 3.6 cm wider waist circumference (P = 0.005) than postmenopausal T347 homozygotes, controlled for covariates. Logistic regression analyses of this polymorphism, adjusted for age, fasting triglyceride, smoking status, alcohol consumption and physical activity disclosed the rare allele to be associated with obesity in postmenopausal women at an odds of 1.80 (95 % CI 1.09-2.97; P = 0.021). Serum apoB level was lower in S347 allele carriers (110.9 ± 2.9 mg/dL) than in T347 homozygotes (119.0 ± 2.4 mg/dL; P = 0.035) in men but not women. APOA4 T347S polymorphism was unrelated to lipids and other lipoproteins in either gender. The APOA4 S347 allele predisposes to obesity and high waist circumference in Turkish postmenopausal women. ApoB levels are lower only in men in S347 allele carriers. Show less

Apolipoprotein C3 (APOC3) gene polymorphisms are associated with cardiometabolic risk factors, varying in ethnicities. This study aimed to investigate such association between the APOC3 -482C>T polymorphism and cardiometabolic risk factors in the turkish adult risk factor (TARF) study cohort, stratifying by gender and obesity. Randomly selected 1548 individuals (757 male and 791 female, mean age 49.9±11.8 years) were genotyped for -482C>T polymorphism using hybridization probes in a Real-Time PCR LC480 device. The -482TT genotype prevailed 9.9% in men and 11.5% in women. Association between 482C>T polymorphism and dyslipidemia (p=0.036, OR=1.42, 95%Cl=1.02-1.97) was found only in men. Analysis of variance showed that anthropometric and metabolic variables were not differently distributed in APOC3 -482C>T genotypes in the study population. In relation to dyslipidemia and obesity, the -482C>T polymorphism showed significant gender-by-genotype interactions (p<0.01). When the study population was stratified according to gender and obesity, homozygotes for the T allele were associated strongly with (by 45%) elevated fasting triglyceride concentrations in obese men (p=0.009) and homeostatic model assessment (HOMA) index in non-obese women (p=0.013). Furthermore, in the same subgroups, the associations of the fasting triglyceride concentrations and HOMA index with the TT genotype remained after adjustment for risk factors (p<0.05). APOC3 -482TT genotype is independently associated with elevated fasting triglyceride concentrations in obese men. Presence of obesity seems to be required for this genotype to induce markedly elevated triglycerides. Furthermore, it is associated with the dyslipidemia in men, without requirement of obesity. Show less

We determined the relationship of smoking status on APOC3 -482C>T polymorphism and apolipoprotein C-III (apoC-III) concentrations and the latter two parameters' influence on risk of diabetes and coronary heart disease (CHD). Prediction of incident cases was assessed at 5.5years' follow-up in unselected 519 individuals of a general population genotyped for -482C>T polymorphism. Female sex and current smoking were significantly associated with low circulating apoC-III in subjects without (p≤0.033) than with abdominal obesity (p=0.053) or than insulin resistant -482TT homozygotes (p=0.034) who had 20-30% higher serum apoC-III. Multi-adjusted serum apoC-III was log-linearly associated with fasting triglycerides. ApoC-III levels determined the development of diabetes [RR 1.56 (95%CI 1.21; 2.01)] and CHD [RR 1.38 (1.10; 1.72) for an increment of 14%], after adjustment for confounders. APOC3 -482TT genotype is associated with high apoC-III concentrations only in the presence of abdominal obesity or insulin resistance, but not in current smokers who remain lean or insulin-sensitive. Rather than APOC3 -482C>T polymorphism, circulating apoC-III determines cardiometabolic risk. Show less