Vitamin D receptor gene polymorphisms and haplotypes (Apa I, Bsm I, Fok I, Taq I) in Turkish psoriasis patients

Abstract

SummaryBackgroundPsoriasis is an inflammatory disease characterized by increased squamous cell proliferation and impaired differentiation. Vitamin D, Calcitriol, and its analogues are successfully used for psoriasis therapy. However, it is unknown why some psoriasis patients are resistant to Vitamin D therapy. Vitamin D mediates its activity by a nuclear receptor. It is suggested that polymorphisms and haplotypes in the VDR gene may explain the differences in response to vitamin D therapy.Material/MethodsIn this study, 102 psoriasis patients and 102 healthy controls were studied for VDR gene polymorphisms. The Fok I, Bsm I, Apa I and Taq I polymorphisms were examined by PCR-RFLP, and 50 subjects received vitamin D therapy to evaluate the association between VDR gene polymorphisms and response to vitamin D therapy. Existence of cutting site is shown by capital letters, and lack was shown by lower case. The haplotypes were analysed by CHAPLIN.ResultsThere was significant difference in allele frequency of T and genotype frequency of Tt between cases and controls (p values 0.038 and 0.04, respectively). The Aa and bb genotypes were significantly higher in early onset than late onset psoriasis (p values 0.008 and 0.04, respectively). The genotypes Ff, ff and TT are significantly different between vitamin D3 therapy responders and non-responders (p values 0.04, 0.0001, 0.009, respectively). To the best of our knowledge, this is the first report showing importance of VDR gene haplotypes in psoriasis, the significance of the Wald and LR (Likelihood Ratio) statistics (p=0,0042) suggest that FfBbAatt is a disease-susceptibility haplotype.ConclusionsHaplotype analysis is a recent and commonly used method in genetic association studies. Our results reveal a previously unidentified susceptibility haplotype and indicate that certain haplotypes are important in the resistance to vitamin D3 therapy and the onset of psoriasis. The haplotypes can give valuable data where genotypes unable to do.

Pooling analysis regarding the impact of human vitamin D receptor variants on the odds of psoriasis

“…Nevertheless, no statistically significant conclusions between VDR rs1544410, rs2228570 and VDR rs731236 polymorphisms and psoriasis susceptibility were observed. The conclusions regarding the genetic effect of VDR rs1544410, rs2228570, but not VDR rs731236 polymorphisms on the odds of psoriasis disease were consistent with the pooling results of Lee, YH [3]., which contains sixteen studies [13,14,[16][17][18][19][20][21][22][24][25][26][27][28][29][30]. Subgroup analysis of "Caucasian" suggested that the VDR rs731236 polymorphism is linked to the risk of psoriasis in the Caucasian population under the recessive model, but not the allele, homozygote and dominant models [3].…”

“…After assessing the eligibility of 85 full-text articles, we removed an additional 67 articles with "expression or non-SNP" data. Finally, we included a total of 18 case-control studies [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] for our metaanalysis. We also summarized and listed the genotypic distribution (Table 1) and clinical characteristics, (Additional file 2: Table S2).…”

Analysis of Vitamin D Receptor (VDR) Gene Polymorphisms in Alopecia Areata

“…The PCR analysis was also performed using a modification of a previously described study [20]. PCR was carried out in a total volume of 25 μl reaction contained, 2.5 mM 10X reaction Buffer, 1.5 mM MgCI2, 0.3 mM dNTP and, 0.8 mol/L of each primer, 1 U of Taq polymerase and approximately 50 ng of genomic DNA.…”

“…PCR products were digested with the restriction en¬zymes (ApaI, TaqI) according to the manufacturer's in¬structions, and restriction fragments of ApaI and TaqI polymorphisms in VDR gene were electrophoresed on an 2% agarose and 1% nusieve agarose gel stained with ethidium bro-mide, and the genotypes were determined under ultraviolet (UV) illumination. ApaI genotypes AA (740 bp), Aa (740, 520, and 220 bp), and aa (520 and 220 bp) and TaqI genotypes: TT (495 and 245 bp), Tt (495, 290, 245, and 205 bp), and tt (290, 245, and 205 bp) [20].…”

Lack of association of vitamin D receptor gene polymorphisms/haplotypes in Sjögren’s syndrome

“…These findings suggest that allelic variations of the VDR gene may partially represent a genetic component associated with the development of autoimmune diseases. Several studies have reported that genetic variations of VDR might be a risk factor for the development of autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), psoriasis, autoimmune thyroid diseases (AITD), type I diabetes (T1D) [19][20][21][22][23][24][25].…”