An association between rs7635818 polymorphism located on chromosome 3p12.3 and the presence of abdominal aortic aneurysm.

The association between gene variant rs7635818 located on chromosome 3p12.3 and abdominal aortic aneurysm (AAA) was not unambiguously determined by the results of genome-wide association studies. The aim of our study was to examine this possible association in the Slovak population, with respect to the presence and severity of AAA.A cross-sectional study was conducted between August 2016 and March 2020. The study included 329 participans, 166 AAA patients and a control group of 163 subjects without confirmed AAA with comparable distribution of genders. The anteroposterior diameter of the abdominal aorta was determined by duplex ultrasonography. AAA was defined as subrenal aortic diameter ≥ 30 mm. DNA samples were genotyped using real-time polymerase chain reaction and subsequent high-resolution melting analysis in presence of unlabelled probe. Genetic models studying the possible association were adjusted to age, sex, smoking, arterial hypertension, diabetes mellitus, creatinine and body mass index (BMI) in multivariate analysis. In the additive model, presence of each C-allele of rs7635818 polymorphism was associated with an almost 50 % increase in probability of developing AAA (OR 1.49; 95 % CI 1.06-2.08; p=0.020). Compared to GG homozygotes, CC homozygotes had more than two times higher risk of developing AAA (OR 2.23; 95 % CI 1.14-4.39; p=0.020). The risk of AAA was also in the recessive model higher for CC homozygotes compared to G-allele carriers (GC/GG) (OR 1.79; 95 % CI 1.01-3.19; p=0.047).The abdominal aortic diameter in CC homozygotes of the rs7635818 polymorphism was 7.66 mm greater compared to GG homozygotes (42.5±22.0 mm vs 34.8±21.3 mm; p=0.022) and 5.88 mm greater compared to G-allele carriers (GC/GG) (42.5±22.0 mm vs 36.6±21.0 mm; p=0.04) in univariate analysis. C-allele variant in rs7635818 G>C polymorphism is associated with a higher probability of developing AAA in the Slovak population.

The effect of alfacalcidiol and metformin on phenotype manifestations in women with polycystic ovary syndrome - a preliminary study.

Aim of this study was to evaluate the effect of vitamin D supplementation in obese, insulin resistant and vitamin D deficient PCOS women on biochemical and clinical hyperandrogenism and menstrual irregularity in comparison to effect of metformin or combined metformin plus vitamin D therapy. Thirty nine PCOS women were randomized into three groups and treated with alfacalcidiol (Group 1), combined alfacalcidiol and metformin therapy (Group 2) and metformin (Group 3) for 6 months. Serum TST, fTST, DHEAS, LH and LH/FSH were measured before and after six months of treatment. Menstrual cycle regularity, hirsutism, acne and pregnancy rate were assessed at the same time. There was a significant decrease in TST levels in the Group 2 and slight but not significant decrease in the Group 3. No significant changes in other parameters (fTST, DHEAS, LH, LH/FSH) have been found after 6 months therapy in all three groups. An improvement of menstrual cycle was detected in 78 % of patients in Group 1 (p<0.04), 80 % in the Group 2 (p<0.03) and in 90 % in the Group 3 (p<0.002), respectively. There was no significant improvement of acne and hirsutism in all three groups (all p not significant). Pregnancy rate was higher in the Group 3 as compared with Groups 1 and 2 (67 % vs. 0 % and 25 %, respectively), however without statistical significance. Vitamin D administration has no significant effect on androgen levels and clinical features of hyperandrogenism in obese vitamin D deficient PCOS women. However, it can potentiate effect of metformin on testosterone levels and LH/FSH ratio but not on clinical hyperandrogenism and pregnancy rate.

A missense variant in GLP1R gene is associated with the glycaemic response to treatment with gliptins.

Gliptins act by increasing endogenous incretin levels. Glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic peptide receptor (GIPR) are their indirect drug targets. Variants of GLP1R and GIPR have previously been associated with the incretin effect. The aim of the present pilot study was to examine associations of the GLP1R and GIPR gene variants with the glycaemic response to gliptins. A total of 140 consecutive patients with type 2 diabetes were followed-up 6 months after initiation of gliptin treatment. GLP1R rs6923761 (Gly168Ser) and GIPR rs10423928 genotyping was performed using real-time PCR, with subsequent high-resolution melting analysis. The main study outcome was reduction in glycated haemoglobin (HbA1c) after treatment. GLP1R Gly168Ser variant was significantly associated with reduction in HbA1c in an additive model (ß = -0.33, p = 0.011). The mean reduction in HbA1c in Ser/Ser homozygotes was significantly lower compared with Gly-allele carriers [0.12 ± 0.23% vs. 0.80 ± 0.09% (1.3 ± 2.5 mmol/mol vs. 8.7 ± 1.0 mmol/mol); p = 0.008]. In conclusion, GLP1R missense variant was associated with a reduced response to gliptin treatment. The genotype-related effect size of ∼0.7% (8 mmol/mol) is equal to an average effect of gliptin treatment and makes this variant a candidate for use in precision medicine.