VDR Polymorphisms in Autoimmune Connective Tissue Diseases: Focus on Italian Population.

Andrea Latini,Roberta Priori,Carlo Perricone,Cinzia Ciccacci,Fulvia Ceccarelli,Giada De Benedittis,Serena Colafrancesco,Fabrizio Conti,Paola Borgiani,Maria Sole Chimenti,Paola Conigliaro,Lucia Novelli,Baohui Xu

doi:10.1155/2021/5812136

Abstract

Vitamin D is an important hormone involved in various physiologic processes, and its activity is linked to binding with vitamin D receptor (VDR). Genetic polymorphisms in the VDR gene could modulate the expression or function of the receptor and, consequently, alter the effects of vitamin D. Variants in VDR gene have been associated with susceptibility to many illnesses sensitive to vitamin D administration and to autoimmune disorders, but no data are available regarding autoimmune connective tissue diseases in Italian population. We analyzed three VDR polymorphisms in 695 Italian patients with autoimmune connective tissue diseases (308 with systemic lupus erythematosus (SLE), 195 with primary Sjogren's syndrome (pSS), and 192 with rheumatoid arthritis (RA)) and in 246 healthy controls with the aim to evaluate a possible association of VDR SNPs with susceptibility to these diseases in the Italian population. Genotyping of rs2228570, rs7975232, and rs731236 in VDR gene was performed by an allelic discrimination assay. A case/control association study and a genotype/phenotype correlation analysis have been performed. We observed a higher risk to develop SLE for rs2228570 TT genotype (P = 0.029, OR = 1.79). No association was observed between susceptibility to pSS or RA and this SNP, although this variant is significantly less present in RA patients producing autoantibodies. For rs7975232 SNP, we observed a significant association of the variant homozygous genotype with SLE (P = 0.009, OR = 1.82), pSS (P = 0.046, OR = 1.66), and RA (P = 0.028, OR = 1.75) susceptibility. Moreover, we reported associations of this genotype with clinical phenotypes of SLE and pSS. Lastly, the GG genotype of rs731236 was associated with a lower RA susceptibility (P = 0.045, OR = 0.55). Our results show that the explored VDR polymorphisms are significantly associated with autoimmune connective tissue disorders and support the hypothesis that the genetic variability of VDR gene may be involved in susceptibility to these diseases in Italian population.

Highlights

Vitamin D is a pleiotropic hormone, which is involved in various physiologic processes, such as phosphate and calcium homeostasis, cell growth, and neuromuscular and immune function [1]
We analyzed three vitamin D receptor (VDR) polymorphisms in 695 Italian patients with autoimmune connective tissue diseases (308 with systemic lupus erythematosus (SLE), 195 with primary Sjogren’s syndrome, and 192 with rheumatoid arthritis (RA)) and in 246 healthy controls with the aim to evaluate a possible association of VDR SNPs with susceptibility to these diseases in the Italian population
Our results show that the explored VDR polymorphisms are significantly associated with autoimmune connective tissue disorders and support the hypothesis that the genetic variability of VDR gene may be involved in susceptibility to these diseases in Italian population

Summary

Introduction

Vitamin D is a pleiotropic hormone, which is involved in various physiologic processes, such as phosphate and calcium homeostasis, cell growth, and neuromuscular and immune function [1]. Genetic polymorphisms in the VDR gene could modulate the expression or function of the receptor and could be involved in the variability of the vitamin D effects [3]. Vitamin D, regulates the maturation of various immune cell lines, such as dendritic cells, monocytes, and activated T and B cells. These cells express VDR gene and respond to the active form of vitamin D [8]. The role of vitamin D in the immune system is well known [14], genetic association studies of VDR SNPs on autoimmune connective tissue diseases in Italian population are lacking

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