Vitamin-D Receptor Genotype and Renal Disorder in Japanese Patients with Systemic Lupus erythematosus

Abstract

Background/Aims: It is known that allelic variants of the gene encoding the vitamin-D receptor (VDR) detected by BsmI increase the risk of some advanced malignant tumors, suggesting that such variants may cause functional differences in 1,25(OH)₂ vitamin D₃. We examined the VDR genes of Japanese systemic lupus erythematosus (SLE) patients, to determine whether different genotypes are correlated with SLE or its criteria. Methods: VDR genotyping of 58 unrelated Japanese SLE patients was performed based on polymerase chain reaction-restriction fragment length polymorphism (RFLP). Following amplification, products were digested with BsmI. The RFLPs were coded as Bb, where the uppercase letter signifies the absence of the digested site and the lowercase letter signifies the presence of the site. Results: The frequency of the VDR BB genotype was significantly higher in SLE patients (15.5%, n = 9/58, p < 0.0001) than in controls (5.7%, n = 5/87). Furthermore, a larger proportion of bb individuals was observed among patients with nephrotic syndrome (61.5%, n = 8/13) than among SLE patients without renal dysfunction (35.7%, n = 10/28). There was a significant tendency for the population of patients with the bb genotype to be correlated with that of patients with renal dysfunction (p = 0.0304). Conclusion: These findings suggest that the BB genotype might trigger the development of SLE, and that the bb genotype is associated with lupus nephritis.

Vitamin D receptor gene <em>Taq</em>I and <em>Apa</em>l polymorphisms and steroid responsiveness in childhood idiopathic nephrotic syndrome

“…Exons 7-9 play a critical role in binding to vitamin D. Allelic variations in VDR are involved in their function, suggesting in turn that allelic variations in VDR cause functional differences in the potency of 1,25-dihydroxy D3 as an immunosuppressive hormone. 19 VDR gene polymorphism (including TaqI and ApaI genotypes) is known to be genetically determined and affected by ethnicity. Our study is considered novel as it is the first of its kind reporting this polymorphism in INS Arab patients from the Middle East region.…”

“…9,11,12 No effects of the different VDR polymorphic genotypes on both chronic kidney disease and end-stage renal disease were previously documented, [20][21][22][23][24][25] whereas studies on systemic lupus erythematosus nephritis, including secondary nephrotic syndrome with or without renal dysfunction, reported an association of renal involvement with the bb genotype of BsmI polymorphism, which is a common single-nucleotide polymorphism of the VDR gene. 19 INS has been widely considered to be a primary immune disease associated with immune regulatory imbalance between Th1 and Th2 cytokines, which are thought to play major roles in the pathogenesis and progression of the disease . 10,[26][27][28] On the other hand, the important role of VDR gene polymorphism in INS could be mediated through its direct effect on the function and potency of 1,25-dihydroxy D3, which is considered an immune suppressor hormone that negatively regulates the production of different cytokines and downregulation of the immune system.…”

Biomarkers in systemic lupus erythematosus: I. General overview of biomarkers and their applicability

“…Other genes implicated in terms of a role in disease susceptibility include Hsp70-2 (in African Americans) (83), IL-4 receptor (84), monocyte chemoattractant protein 1 (85), plasminogen activator inhibitor 1 (86,87) ␤ 2 -glycoprotein I (88), osteopontin (89), vitamin D receptor (90), Ets (91), DNase (92), and prolactin (93).…”

Vitamin D Receptor (VDR) mRNA and VDR Protein Levels in Relation to Vitamin D Status, Insulin Secretory Capacity, and VDR Genotype in Bangladeshi Asians

“…At least 22 unique nonfunctional VDR variants have been described, most of which lead to rare syndromes associated with vitamin D-resistant rickets (4). A number of common chronic disorders of inflammatory, infective, and autoimmune etiologies, including both type 1 and type 2 diabetes and colorectal adenoma, have been shown to be associated with specific polymorphisms of the vitamin D receptor gene, although not all such associ-ations are found consistently in different populations (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”