The efficacy of calcitriol treatment in non-alcoholic fatty liver patients with different genotypes of vitamin D receptor FokI polymorphism

Background Vitamin D deficiency is prevalent in patients with non-alcoholic fatty liver disease (NAFLD), but there are debates on the usefulness of vitamin D treatment. The interindividual variations in response may be due to different genetic backgrounds. The present study evaluated the efficacy of calcitriol treatment in NAFLD patients with regard to the vitamin D receptor (VDR) genotypes of FokI polymorphism. Methods The study was conducted on 128 NAFLD patients randomly divided into two groups and were subjected to intervention with 0.25 mcg calcitriol/day or placebo for 4 months, while anthropometric parameters, glycemic status, lipid profiles, inflammatory markers, liver enzymes, and fatty liver indices were measured. The ARMS-PCR method was used to genotype the VDR FokI polymorphism. Results Calcitriol treatments along with weight loss and diet recommendations decreased the liver enzymes (AST, ALT, and ALP, p < 0.001 for all) and fatty liver indices (HSI, p < 0.01 and APRI, p < 0.001), compared to the baseline. But when the calcitriol effects were compared to the placebo group, only ALP decrease remained significant (17.5 IU. P = 0.02). The prevalent FokI variants in our population were FF (53.1%) and Ff genotype (45.3%). No significant interaction of FokI variants to the calcitriol effects was found except for ALP. The decrease in the ALP activity was higher in calcitriol-received patients with the Ff genotype (p = 0.05). Conclusions The FF and Ff variants of VDR FokI polymorphism did not interact with the effects of calcitriol on fatty liver, but the ALP was more responsive in subjects with the Ff variant. IRCT registration number IRCT2017053034222N1 Registration date: 2017-06-28 - Retrospectively registered, https://en.irct.ir/trial/26203

Association Between Vitamin D Levels and Vitamin D Receptor FokI Polymorphism in Thai Postmenopausal Women With Osteoporosis

Background: Osteoporosis is a complex genetic disease, which is common among postmenopausal women. It is characterized by decreased bone mineral density (BMD) and increased bone fragility and fractures. Objective: To study the association between serum vitamin D levels and vitamin D receptor (VDR) genetic FokI polymorphism in postmenopausal women with osteoporosis. Methods: A total of 60 postmenopausal women who came for treatment at the menopausal clinic at Ramathibodi Hospital were enrolled. All of the patients had their BMD measured, and were determined serum vitamin D levels and VDR FokI polymorphism. Data were analyzed using chi-square and Fisher exact tests. The frequency of single nucleotide polymorphism (SNP) with risk of osteoporosis was compared. Results: Among 60 postmenopausal women, 26 (43.3%) women were an osteoporotic group and 34 (56.7%) women were non-osteoporotic group. There were no significant differences in age, vitamin D levels, or VDR FokI polymorphism between the groups (P > .05). However, the TT genotype of VDR FokI polymorphism was significantly associated with vitamin D deficiency (< 20 ng/mL) (OR, 6.15; 95% CI, 1.51 - 25.14; P < .05). Conclusions: Vitamin D levels and genotype of VDR FokI polymorphisms were similar between the osteoporotic and non-osteoporotic postmenopausal women. The TT genotype of VDR FokI polymorphism showed a significant association with vitamin D deficiency. Therefore, TT genotype of VDR FokI polymorphism may be used to predict risk of vitamin D deficiency.

VDR Gene Polymorphisms in Healthy Individuals with Family History of Premature Coronary Artery Disease

Aim. The gene encoding the vitamin D receptor (VDR) is considered in many studies to be a good candidate responsible for susceptibility to several diseases such as coronary artery disease (CAD). Epidemiological data show that cardiovascular disease is one of the major health problems in Polish society. Basic studies show that genetic factors play a significant role in the pathogenesis of CAD. We conducted this clinical study to determine if the VDR gene polymorphisms TaqI (rs731236), ApaI (rs7975232), and FokI (rs2228570) could predispose healthy individuals to an increased risk of premature CAD (P-CAD) incidents. Methods. We genotyped 845 subjects in a cohort consisting of 386 healthy volunteers with a documented P-CAD incident in their first-degree relatives and 459 healthy volunteers without family history (FH) of P-CAD. TaqI, ApaI, and FokI polymorphisms in VDR were genotyped using TaqMan assays and the endpoint genotyping method (qPCR). Statistical analyses were performed using the Power Analysis Software STATISTICA v.13.3. Results. Although no statistical significance was found for TaqI and ApaI genotype frequencies, the AA genotype of FokI polymorphism was significantly more frequent in the study group compared to the control group (24.61% vs. 16.99%). The results of logistic regression analysis suggested a significant association between FokI polymorphism and FH of P-CAD in heathy people under the recessive model (OR: 1.26 (1.07-1.49, p = 0.007 )); however, the frequency of VDR haplotypes did not differ significantly between the control and study populations. Conclusions. FokI polymorphism is may be associated with FH of P-CAD. FokI polymorphism may predispose to the development of P-CAD among healthy people over the next years.

Artificial Neural Networks Model for Predicting Type 2 Diabetes Mellitus Based on VDR Gene FokI Polymorphism, Lipid Profile and Demographic Data

Type 2 diabetes mellitus (T2DM) is a multifactorial disease associated with many genetic polymorphisms; among them is the FokI polymorphism in the vitamin D receptor (VDR) gene. In this case-control study, samples from 82 T2DM patients and 82 healthy controls were examined to investigate the association of the FokI polymorphism and lipid profile with T2DM in the Jordanian population. DNA was extracted from blood and genotyped for the FokI polymorphism by polymerase chain reaction (PCR) and DNA sequencing. Lipid profile and fasting blood sugar were also measured. There were significant differences in high-density lipoprotein (HDL) cholesterol and triglyceride levels between T2DM and control samples. Frequencies of the FokI polymorphism (CC, CT and TT) were determined in T2DM and control samples and were not significantly different. Furthermore, there was no significant association between the FokI polymorphism and T2DM or lipid profile. A feed-forward neural network (FNN) was used as a computational platform to predict the persons with diabetes based on the FokI polymorphism, lipid profile, gender and age. The accuracy of prediction reached 88% when all parameters were included, 81% when the FokI polymorphism was excluded, and 72% when lipids were only included. This is the first study investigating the association of the VDR gene FokI polymorphism with T2DM in the Jordanian population, and it showed negative association. Diabetes was predicted with high accuracy based on medical data using an FNN. This highlights the great value of incorporating neural network tools into large medical databases and the ability to predict patient susceptibility to diabetes.