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

Abstract

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

Vitamin D-related Genetic Variations and Non-alcoholic Fatty Liver Disease: a Systematic Review

“…A total of 19 records were further excluded at this stage since they did not report the outcome of interest. Finally, a total of 12 studies fulfilled the eligibility criteria [20][21][22][23][24][25][26][27][28][29][30][31].…”

“…A total of 12 studies consisting of at least 18,012 participants combined reported the outcome of interest [20][21][22][23][24][25][26][27][28][29][30][31]. These studies were conducted in 2010 to 2022.…”

“…These studies were conducted in 2010 to 2022. Four studies (two from the same population) are from China [26][27][28]31], three studies from the same group are from the United Kingdom [22][23][24], and the rest are from Australia [20], Germany, Iran [29], Japan [21] and United States [30]. The average age of participants varied from 13.8 to 55.0 years and the percentage of females varied from 16.7 to 60.0%.…”

“…Five studies investigated the association between vitamin D-related genetic variations and presence of NAFLD [20,22,26,30,31], while 6 studies explored the relationship between the genetic variations and severity of NAFLD [22][23][24][25]30] and one study explored the influence of VDR genetic variation on response to calcitriol treatment [29]. Evaluations of NAFLD were performed by liver ultrasound in five studies [20,[27][28][29]31], liver biopsy in four studies [21][22][23][24] and abdominal computed tomography in one study [30]. Eight of the 12 studies were of high quality based on Newcastle Ottawa score of more than seven [20,21,[25][26][27][28]30,31].…”

“…Interestingly, variations of genes involved in vitamin D metabolism pathway described above have been shown to be associated with many conditions, such as coronary artery disease, osteoporosis, diabetes and autoimmune diseases, indicating the interaction between this pathway and health outcomes [16][17][18][19]. Additionally, a number of studies have reported the association between vitamin D-related genetic variations and NAFLD [20][21][22][23][24][25][26][27][28][29][30][31]. The objective of this systematic review was therefore to identify and summarize the results of all available studies that explored the association of vitamin D-related genetic polymorphisms with presence, severity and response to treatment of NAFLD.…”