Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Alimentary Tract Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
BMC Pharmacol Toxicol. 2021 Apr 7;22(1):18. doi: 10.1186/s40360-021-00485-y.
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.
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.
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).
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.
IRCT2017053034222N1 Registration date: 2017-06-28 - Retrospectively registered, https://en.irct.ir/trial/26203.
非酒精性脂肪性肝病（NAFLD）患者普遍存在维生素 D 缺乏，但维生素 D 治疗的有效性仍存在争议。这种个体间的反应差异可能与不同的遗传背景有关。本研究评估了维生素 D 受体（VDR）FokI 多态性基因型对 NAFLD 患者使用骨化三醇治疗的疗效。
本研究纳入 128 例 NAFLD 患者，随机分为两组，分别给予 0.25 mcg 骨化三醇/天或安慰剂治疗 4 个月，同时测量人体测量参数、血糖状态、血脂谱、炎症标志物、肝酶和脂肪肝指数。采用 ARMS-PCR 法检测 VDR FokI 多态性基因型。
与基线相比，骨化三醇治疗联合体重减轻和饮食建议可降低肝酶（AST、ALT 和 ALP，均 P<0.001）和脂肪肝指数（HSI，P<0.01 和 APRI，P<0.001）。但与安慰剂组相比，只有 ALP 降低有统计学意义（17.5 IU，P=0.02）。本研究人群中最常见的 FokI 变体为 FF（53.1%）和 Ff 基因型（45.3%）。除 ALP 外，未发现 FokI 变体与骨化三醇作用的显著相互作用。在接受骨化三醇治疗的患者中，Ff 基因型的 ALP 活性下降更高（P=0.05）。
VDR FokI 多态性的 FF 和 Ff 变体与骨化三醇对脂肪肝的作用无相互作用，但 Ff 变体的 ALP 更敏感。
IRCT 注册号：IRCT2017053034222N1 注册日期：2017-06-28 - 回顾性注册，https://en.irct.ir/trial/26203.
