维生素D缺乏及维生素D受体基因多态性与1型糖尿病风险的关联：一项南印度家族性研究

Association of Vitamin D Deficiency and Vitamin D Receptor Gene Polymorphisms with Type 1 Diabetes Risk: A South Indian Familial Study.

作者信息

Thirunavukkarasu Ramasamy, Chitra Ayyappan, Asirvatham Arthur, Jayalakshmi Mariakuttikan

机构信息

Madurai Kamaraj University School of Biological Sciences, Department of Immunology, Madurai, India

Government Rajaji Hospital, Institute of Child Health and Research Centre, Madurai, India

出版信息

J Clin Res Pediatr Endocrinol. 2024 Mar 11;16(1):21-30. doi: 10.4274/jcrpe.galenos.2023.2022-12-7. Epub 2023 Aug 10.

DOI:10.4274/jcrpe.galenos.2023.2022-12-7

PMID:37559366

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10938518/

Abstract

OBJECTIVE

Vitamin D is a potent immune modulator and is associated with autoimmune diseases, including type 1 diabetes (T1D). The vitamin D levels and its receptor gene polymorphisms together in T1D are not yet investigated in the South Indian population. The present study focused on exploring the significance of vitamin D levels and vitamin D receptor (VDR) gene polymorphisms with the risk of developing T1D in the South Indian population.

METHODS

Patients with T1D and unaffected first-degree relatives (FDRs) were included in this study. Genotyping of VDR polymorphisms at four different loci (FokI- F/f, BsmI- B/b, TaqI- T/t, and ApaI- A/a) was assessed through the amplification refractive mutation system-polymerase chain reaction method. Serum vitamin D levels were measured in 98 T1D patients and 75 age- and sex-matched siblings.

RESULTS

A total of 120 patients with T1D and 214 FDRs were included. Vitamin D deficiency (VDD) was observed in a higher proportion of T1D patients than in controls (52% vs. 32%; p<0.03). The frequency of the FokI-FF genotype was significantly higher [odds ratio (OR)=1.66; p<0.03] in T1D patients conferring a susceptible association with the disease. Nevertheless, the increased frequency of heterozygous Ff genotype (OR=0.57; p<0.02) among controls may confer a protective association with T1D. Furthermore, the transmission disequilibrium test revealed over-transmission of ApaI-A (T: U=15/5; p<0.006) and BsmI-B alleles (T: U=17/5; p<0.01) and under-transmission of BsmI-b/ApaI-a/TaqI-T haplotype (T: U=5.4/14.4; p=0.04) from parents to T1D patients.

CONCLUSION

The present study concludes that VDD is the major contributing risk factor to T1D development in the South Indian population. Furthermore, the FokI-FF genotype, BsmI-B, and ApaI-A alleles were positively associated with T1D. In contrast, the FokI-Ff genotype and BsmI-b/ApaI-a/TaqI-T haplotype were negatively associated with T1D.

摘要

目的

维生素D是一种强大的免疫调节剂，与包括1型糖尿病（T1D）在内的自身免疫性疾病有关。在南印度人群中，尚未对T1D患者的维生素D水平及其受体基因多态性进行联合研究。本研究着重探讨维生素D水平和维生素D受体（VDR）基因多态性在南印度人群中与T1D发病风险的关系。

方法

本研究纳入了T1D患者及未患病的一级亲属（FDRs）。通过扩增折射突变系统-聚合酶链反应法评估四个不同位点（FokI - F/f、BsmI - B/b、TaqI - T/t和ApaI - A/a）的VDR多态性基因分型。对98例T1D患者及75例年龄和性别匹配的同胞进行血清维生素D水平检测。

结果

共纳入120例T1D患者和214例FDRs。T1D患者中维生素D缺乏（VDD）的比例高于对照组（52%对32%；p<0.03）。T1D患者中FokI - FF基因型的频率显著更高[比值比（OR）=1.66；p<0.03]，表明与该病存在易感性关联。然而，对照组中杂合子Ff基因型频率增加（OR=0.57；p<0.02），可能与T1D存在保护性关联。此外，传递不平衡检验显示，从父母到T1D患者，ApaI - A（T:U = 15/5；p<0.006）和BsmI - B等位基因过度传递（T:U = 17/5；p<0.01），而BsmI - b/ApaI - a/TaqI - T单倍型传递不足（T:U = 5.4/14.4；p = 0.04）。