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

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.

Involvement of the secosteroid vitamin D in autoimmune rheumatic diseases and COVID-19

“…Selected VDR polymorphisms have been found to be associated with autoimmune connective tissue disorders, supporting the hypothesis that genetic variability of the VDR gene and vitamin D–cell interactions could be involved in susceptibility to ARDs such as RA 22 . Similarly, a number of interactions between long non-coding RNAs and VDR have been detected, and some long non-coding RNAs can alter VDR expression and/or transcriptional activity and vitamin D signalling 23 .…”

The impact of genetic variants related to vitamin D and autoimmunity: A systematic review

“… Addison's disease Fichna, M., 2009 [ 222 ] Poland Case-Control 101/251 35,8/59,4 PCR-RFLP No CYP27B1 rs10877012 There was a prevalence of the C (rs10877012) allele in patients with AAD than in the control group, as well as the frequency of the 'CC' genotype, tending to be 2-fold as likely to develop AAD than other genotypes. Alopecia Areata Ates, O., 2017 [ 223 ] Turkey Case-Control 198/167 32.62 ± 9.621/31.56 ± 11.319 PCR-RFLP No VDR Bsm I (rs1544410); Apa I (rs7975232) and Taq I (rs731236) No association was found between the genetic variants studied and the genetics of Alopecia Areata Autoimmune Connective Tissue: systemic lupus erythematosus, primary Sjogren's syndrome, and with rheumatoid arthritis Latini A, 2021 [ 64 ] Italy Case-Control SLE 308, pSS 195, RA 92/246 NA TaqMan Genotyping Assay No VDR rs2228570, rs7975232 and rs731236 For rs7975232 SNP, it was observed a significant association of the variant homozygous genotype with SLE, pSS, and RA susceptibility. Moreover, it reported associations of this genotype with clinical phenotypes of SLE and pSS.…”

MicroRNA-125b mediates Interferon-γ-induced downregulation of the vitamin D receptor in systemic lupus erythematosus

“…The VD/VDR cascade in immune cells has been implicated in regulating the balance of the immune system and in prevention of substantial autoimmune diseases, including SLE [ 12 , 24 , 28 , 29 ]. Emerging evidence indicates that VDR signaling regulates the expression of inflammatory factors, which may play a protective role in SLE.…”