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Evaluating Associations Between Ankylosing Spondylitis, Torque Teno Virus and Polymorphisms in Interleukin 6 and Vitamin D Receptor Genes.

The etiology of ankylosing spondylitis (AS) is complex and not yet fully understood. Interleukin-6 (IL-6), vitamin D and the vitamin D receptor (VDR) play an important role in modulating immune response, and Torque teno virus is considered a marker of immune status. This case-control study aimed to investigate the predisposition to AS. A total of 85 patients with AS and 100 clinically healthy individuals were included. VDR polymorphisms (rs2228570, rs1544410, rs7975232, rs731236) were genotyped using the PCR-RFLP technique, while for the IL-6 -174 G>C (rs1800795) polymorphism the tetra-primer ARMS-PCR technique was used. The presence of TTV was detected using the hemi-nested PCR technique. Our findings indicate a statistically significant association between TTV and AS (p = 0.035). C allele of both rs1800795 polymorphism in main groups (p = 0.027) and rs731236 polymorphism in women subgroups (p = 0.036) may be linked to an increased susceptibility to AS. However, none of these associations reach statistical significance after Bonferroni correction. Furthermore, within female subgroups, a significant association was found between the T allele of rs1544410 polymorphism and AS (p = 0.000038, corrected p = 0.00076). A significant association was also observed between the TT genotype of rs2228570 polymorphism, TTV and AS (p = 0.029). Haplotype analysis revealed that certain VDR haplotypes may confer either a protective effect against AS or an increased risk of developing the condition. Notably, rs1544410 polymorphism or a linked polymorphism may influence AS susceptibility. In conclusion, our data suggest that TTV and VDR polymorphisms may be associated with an increased risk of developing AS, indicating that these markers could potentially be used in the future for earlier diagnosis and more targeted treatment of the disease.

Torque teno virus↗

The association between vitamin D receptor gene polymorphism FokI and type 2 diabetic kidney disease and its molecular mechanism: a case control study.

BACKGROUND: The role of the vitamin D receptor single nucleotide polymorphism FOKI (VDR-FOKI) (rs2228570) in genetic susceptibility to type 2 diabetic kidney disease (T2DKD) remains uncertain. This study investigated the relationship between VDR-FOKI and T2DKD within the Chinese Plateau Han population and analyzed the underlying mechanisms. METHODS: A total of 316 subjects were enrolled, including 44 healthy adults, 114 individuals with type 2 diabetes mellitus (T2DM), and 158 patients with T2DKD. According to the 2023 American Diabetes Association Diabetes Guidelines, patients with T2DKD were categorized into low-medium-risk and high-risk groups based on estimates of glomerular filtration rate and urinary albumin-to-creatinine ratio. The VDR-FokI genotypes of all participants were identified using the Taqman probe and classified as homozygous mutant genotypes (C/C or FF), heterozygous mutant genotypes (C/T or Ff), and homozygous wild genotypes (T/T or ff). Plasma levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase activity (SOD) were assessed in T2DKD patients with FF and ff genotypes. Additionally, the levels of plasma VDR, GPX4, and P53 were determined using ELISA, while the relative expressions of VDR mRNA, GPX4 mRNA, and TP53 mRNA in whole blood were measured by RT-qPCR. RESULTS: The T2DM patients with the ff genotype exhibited a 2.93-fold increased likelihood of developing T2DKD compared to those with the FF genotype (ORadjusted = 2.93; 95% CI: 1.142-7.513). Additionally, they were 2.01 times more likely to develop T2DKD than individuals with the FF and Ff genotypes (ORadjusted = 2.01; 95% CI: 1.008-4.006). However, no significant differences in VDR-FokI genotype distribution were observed between the healthy control group and the T2DM group, as well as between the low-medium-risk and high-risk groups of T2DKD. Furthermore, T2DKD patients with the ff genotype had significantly higher plasma levels of MDA compared to those with the FF genotype. In contrast, plasma GSH and SOD content was significantly lower in the ff genotype patients (P&#x2009;<&#x2009;0.05). Additionally, the GPX4 concentration in ff genotype patients was significantly lower than in FF genotype patients [14.88 (11.32,22.39) vs. 12.76 (8.55,13.75), P&#x2009;=&#x2009;0.037]. Nevertheless, no statistically significant difference was observed in the expression of VDRmRNA, GPX4mRNA, TP53mRNA, plasma VDR, and plasma P53. CONCLUSIONS: The ff genotype of VDR-FokI is a risk factor for T2DKD, and the potential mechanism may be related to ferroptosis. However, It is not associated with T2DM or the progression of T2DKD.

Humans↗

The short vitamin D receptor is associated with increased risk for generalized aggressive periodontitis.

BACKGROUND: Generalized aggressive periodontitis (GAP) exhibits severe inflammation and alveolar bone loss. Vitamin D receptor (VDR) regulates both bone metabolism and inflammation-related genes, and its polymorphisms and haplotypes may affect the functional activity of the VDR protein in GAP. OBJECTIVE: We analysed the genetic effect of VDR start codon, intron, and exon polymorphisms, and their haplotypes on the development of GAP. MATERIALS AND METHODS: The VDR start codon 27823C > T (rs2228570, FokI), intron 8 60890G > A (rs154410, BsmI), and exon 9 61968T > C (rs731236, TaqI) polymorphisms were determined by using the polymerase chain reaction-restriction fragment length polymorphism analysis among 93 GAP patients and 143 healthy controls. RESULTS: The VDR start codon 27823*C/*C genotype was associated with an increased risk for GAP [odds ratio (OR) = 1.83, p = 0.028], but the intron 8 60880G > A and exon 9 61968T > C polymorphisms were not associated with GAP. The VDR haplotype homozygote ht1(C-G-T) carrying 27823*C allele was associated with a 1.8-fold increased risk of GAP (OR = 1.84, p = 0.030). CONCLUSION: These results demonstrate that the short VDR (27823*C/*C) protein may influence GAP susceptibility.

Adenine↗