Vitamin D Receptor FokI Rs2228570 Research Articles

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

Previous studies have produced inconsistent results regarding the contribution of single-nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene to ovarian cancer (OC) in various ethnicities. Additionally, little has been established with regard to the role of SNPs located in the retinoid X receptor α (RXRA), vitamin D-binding protein [also know as group-specific component (GC)] and VDR genes in non-carriers of the breast cancer 1/2 early onset (BRCA1/BRCA2) gene mutations. All participating individuals in the present study were evaluated for BRCA1 mutations (5382incC, C61G and 4153delA) with HybProbe assays, and for BRCA2 mutation (5946delT) using high-resolution melting (HRM) analysis. The associations of 8 SNPs located in RXRA, GC and VDR were investigated in OC patients without the BRCA1/BRCA2 mutations (n=245) and healthy controls (n=465). Genotyping of RXRA rs10881578 and rs10776909, and GC rs1155563 and rs2298849 SNPs was conducted by HRM analysis, while RXRA rs749759, GC rs7041, VDR BsmI rs1544410 and FokI rs2228570 genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. In addition, the gene-gene interactions among all tested SNPs were studied using the epistasis option in PLINK software. The lowest P-values of the trend test were identified for VDR rs1544410 and GC rs2298849 as Ptrend=0.012 and Ptrend=0.029, respectively. It was also found that, in the dominant inheritance model, VDR BsmI contributed to an increased risk of OC [odds ratio (OR), 1.570; 95% confidence interval (CI), 1.136-2.171; P=0.006; Pcorr=0.048]. The gene-gene interaction analysis indicated a significant interaction between RXRA rs749759 and VDR FokI rs2228570 (OR for interaction, 1.687; χ2=8.278; asymptotic P-value=0.004; Pcorr=0.032). In conclusion, this study demonstrated that certain VDR and RXRA SNPs may be risk factors for OC in non-carriers of BRCA1/BRCA2 mutations in the Polish population.

Relationship between vitmin D receptor rs2228570 polymorphism and susceptibility to gout in Chinese Han male population

Objective To explore gene polymorphism of G/A genotype of FokⅠrs2228570(G/A)of vitamin D receptor(VDR)gene in Han male population of Chinese coastal area, and thus to investigate the relationship between the gene polymorphism of VDR and gout. Methods Altogether 504 gout patients and 523 healthy controls were enrolled. The possible association between the polymorphism of VDR rs2228570 and gout in Chinese coastal area was investigated and genotype frequencies and allelic frequencies were calculated by realtime PCR with Taqman® probe method. Hardy-Weinberg was used to verify the representativeness of the sample. Comparison between the groups were performed with χ2 test and t-test. Results The frequencies of GG, AG, and AA genotypes were 32.1%, 50.0%, and 17.9%, respectively among gout patients, while they were 27.9%, 50.5%, and 21.6% respectively among the controls. There was no statistically significant difference in VDR rs2228570 genotype frequencies between gout patients and controls(χ2=3.366, P>0.05). The allele frequencies of G and A in gout cases were different from those in the controls(57.1%, 42.9%; 53.2%, 46.8%; χ2=3.300, P>0.05). Conclusions Results of the present study suggest that the G/A genotype of VDR FokⅠrs2228570 of the VDR gene is not associated with gout in male population of Chinese coastal area. (Chin J Endocrinol Metab, 2015, 31: 316-319) Key words: Vitmin D receptor; Polymorphism, single Nucleotide; Gout