泰国人群中维生素D受体基因在代谢综合征及相关疾病中的遗传变异

Genetic variations of vitamin D receptor gene in metabolic syndrome and related diseases in the Thai population.

作者信息

Karuwanarint Piyaporn, Phonrat Benjaluck, Tungtrongchitr Anchalee, Suriyaprom Kanjana, Chuengsamarn Somlak, Tungtronchitr Rungsunn

机构信息

Department of Tropical Nutrition & Food Science, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

出版信息

Asia Pac J Clin Nutr. 2018;27(4):935-944. doi: 10.6133/apjcn.122017.04.

DOI:10.6133/apjcn.122017.04

PMID:30045441

Abstract

BACKGROUND AND OBJECTIVES

The genetic variations of vitamin D receptor (VDR) have revealed its association with the risk of metabolic syndrome (MetS). In Thailand, evidence of this association has not been obtained. Thus, this study aimed to investigate the association of VDR gene polymorphism with MetS and related diseases as well as the possible linkage disequilibrium (LD) and haplotypes of VDR in Thai adults.

METHODS AND STUDY DESIGN

Four single nucleotide polymorphisms (SNPs) of VDR gene, rs2228570, rs1544410, rs7975232 and rs731236, were genotyped using PCR-RFLP method in 259 MetS and 261 control groups.

RESULTS

Genotypes AA of rs1544410, TG of rs7975232 and TG+TT of rs7975232 were significantly associated with an increased risk of MetS [OR 10.8 (2.07-56.1), p=0.005], [OR 1.83 (1.16-2.87), p=0.009] and [OR 1.78 (1.17-2.72), p=0.007], respectively, using GG as a reference. Moreover, genotype AA of rs1544410 showed a strong association compared with GG+AG [OR 11.4 (2.20-59.2), p=0.004]. Diseases related to MetS also had significant associations with two SNPs of the VDR gene (rs1544410 and rs7975232). In addition, LD among rs1544410, rs7975232 and rs731236 was detected. Haplotype CATT significantly increased the risk of MetS [OR 4.32 (1.32- 14.1), p=0.016], although haplotype TGGT reduced the risk [OR 0.68 (0.48-0.98), p=0.042].

CONCLUSIONS

The SNPs rs1544410 and rs7975232 were mainly implicated in the increased risk of MetS in the Thai population. LD and haplotypes of VDR gene related to MetS were also discovered. These SNPs of VDR gene are remarkable genetic factors involved in the development of MetS.

摘要

背景与目的

维生素D受体（VDR）的基因变异已显示出其与代谢综合征（MetS）风险的关联。在泰国，尚未获得这种关联的证据。因此，本研究旨在调查VDR基因多态性与MetS及相关疾病的关联，以及泰国成年人中VDR可能存在的连锁不平衡（LD）和单倍型。

方法与研究设计

采用PCR-RFLP方法对259例MetS患者和261例对照组进行VDR基因的4个单核苷酸多态性（SNP），即rs2228570、rs1544410、rs7975232和rs731236的基因分型。

结果

以GG为参照，rs1544410的AA基因型、rs7975232的TG基因型以及rs7975232的TG+TT基因型与MetS风险增加显著相关，其比值比（OR）分别为10.8（2.07 - 56.1），p = 0.005；[OR 1.83（1.16 - 2.87），p = 0.009]和[OR 1.78（1.17 - 2.72），p = 0.007]。此外，与GG+AG相比，rs1544410的AA基因型显示出更强的关联性[OR 11.4（2.20 - 59.2），p = 0.004]。与MetS相关的疾病也与VDR基因的两个SNP（rs1544410和rs7975232）存在显著关联。此外，检测到rs1544410、rs7975232和rs731236之间存在LD。单倍型CATT显著增加了MetS风险[OR 4.32（1.32 - 14.1），p = 0.016]，而单倍型TGGT则降低了风险[OR 0.68（0.48 - 0.98），p = 0.042]。