Vitamin D receptor geneBsmIpolymorphism B allele, but not BB genotype, is associated with systemic lupus erythematosus in a Han Chinese population

Abstract

The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to autoimmune disorders. Association studies of VDR polymorphisms and risk of systemic lupus erythematosus (SLE) have often produced conflicting results in different ethnic backgrounds. The aim of this study is to test the association between VDR gene BsmI polymorphism and the genetic susceptibility to SLE in a Han Chinese population. Three hundred and thirty-seven patients with SLE and 239 healthy controls were genotyped for the VDR gene BsmI polymorphism (rs1544410) by polymerase chain reaction and restriction fragment length polymorphism analysis in this study, after which the relationship between BsmI polymorphisms and the mRNA expression of VDR, as well as clinical manifestations in patients with SLE, was evaluated. It was found that the frequency of B allele was significantly increased in SLE relative to the control group (χ(2) = 4.681, p = 0.031), although the distribution of VDR BsmI polymorphism genotype frequencies did not differ significantly between patients and controls (χ(2) = 4.098, p = 0.129). Moreover, VDR B allele was found to be associated with lupus nephritis (p = 0.027) and also with production of anti-nucleosome antibodies (p = 0.037). The mRNA of VDR was markedly down-regulated in patients with VDR B allele compared with that in patients without B allele (p = 0.016). Our results indicate a possible role of genetic factors (the VDR B allele) in influencing disease susceptibility in Han Chinese patients. Also, VDR B allele is associated with the development of nephritis and the down-regulation of VDR mRNA expression in SLE.

Vitamin D Receptor Gene BsmI and FokI Polymorphisms in Relation to Ovarian Cancer Risk in the Polish Population

“…The BsmI SNP may be associated with the different length polyadenylate sequence within the 3¢-untranslated region of the VDR gene (Uitterlinden et al, 2004). Recently, studies conducted by Luo et al (2012) have indicated that the level of VDR mRNA was remarkably reduced in patients with the VDR BsmI A (B) allele versus individuals bearing the GG (bb) genotype (Luo et al, 2012).…”

“…The effects of BsmI and FokI SNPs on the VDR protein function have already been studied (Arai et al, 1997;Luo et al, 2012;Monticielo et al, 2012). The FokI SNP situated in exon 2 results in the formation of a second methionine start site that leads to the production of a shorter protein receptor (Arai et al, 1997).…”

Polymorphic variants in vitamin D signaling pathway genes and the risk of endometriosis-associated infertility

“…The function of BsmI and FokI SNPs on the biological effects of VDR have been extensively studied (18,(32)(33)(34). The BsmI polymorphism may change the length of the polyadenylate sequence in VDR transcript (18 significantly reduced the mRNA expression levels of VDR in carriers of the A (B) allele, as compared with subjects carrying the GG (bb) genotype (32).…”

“…The BsmI polymorphism may change the length of the polyadenylate sequence in VDR transcript (18 significantly reduced the mRNA expression levels of VDR in carriers of the A (B) allele, as compared with subjects carrying the GG (bb) genotype (32). The FokI SNP gives rise to two protein forms: A long VDR, encoded by the minor allele form (ATG; f), which contains three additional amino acids, and a shorter form, encoded by (ACG; F) (33).…”

Polymorphic variants in the vitamin D pathway genes and the risk of ovarian cancer among non-carriers of BRCA1/BRCA2 mutations

“…The possible role of BsmI and FokI polymorphisms on the action of VDR have been demonstrated elsewhere (8,(49)(50)(51). The BsmI SNP may alter the length of the polyadenylate sequence within the 3'-untranslated region of the VDR gene (8).…”