Exonic variants of genes related to the vitamin D signaling pathway in the families of familial multiple sclerosis using whole‐exome next generation sequencing

Abstract

Introduction Vitamin D (VD) deficiency has been associated with multiple sclerosis (MS) and other autoimmune diseases (AIDs). However, the effect of the genetics of VD on the risk of MS is subject to debate. This study focuses on genes linked to the VD signaling pathway in families with MS. The evaluation of gene variants in all the members of families could contribute to an additional knowledge on the information obtained from case‐control studies that use nonrelated healthy people. Material and Methods We studied 94 individuals from 15 families including at least two patients with MS. We performed whole‐exome next generation sequencing on all individuals and analyzed variants of the DHCR7, CYP2R1, CYP3A4, CYP27A1, GC, CYP27B1, LRP2, CUBN, DAB2, FCGR, RXR, VDR, CYP24A1, and PDIA3 genes. We also studied PTH, FGF23, METTL1, METTL21B, and the role of the linkage disequilibrium block on the long arm of chromosome 12, through analysis of the CDK4, TSFM, AGAP2, and AVIL genes. We compared patients with MS, other AIDs and unaffected members from different family types. Results The study described the variants in the VD signaling pathway that appear in families with at least two patients with MS. Some infrequent variants were detected in these families, but no significant difference was observed between patients with MS and/or other AIDs and unaffected family members in the frequency of these variants. Variants previously associated with MS in the literature were not observed in these families or were distributed similarly in patients and unaffected family members. Conclusion The study of genes involved in the VD signaling pathway in families that include more than one patient with MS did not identify any variants that could explain the presence of the disease, suggesting that VD metabolism could probably play a role in MS more as an environmental factor rather than as a genetic factor. Our study also supports the analysis of cases and unaffected individuals within families in order to determine the influence of genetic factors.

ACE2, TMPRSS2, and Furin variants and SARS‐CoV‐2 infection in Madrid, Spain

“…The WES methodology followed is published elsewhere, 30 but is also included in the Supplemental material. Sequencing information is included in the European Genome‐Phenome Archive.…”

Whole-Exome Sequencing for Identification of Genetic Variants Involved in Vitamin D Metabolic Pathways in Families With Vitamin D Deficiency in Saudi Arabia

“…With regard to GC (rs9016) and LRP2 (rs4667591), no reports exist in the literature about their relationship with vitD. However, these two SNPs were reported in a family-based WES study specifically looking at SNPs in genes related to vitD metabolism in families with familial multiple sclerosis; however, no association was found with multiple sclerosis ( Pytel et al, 2019 ).…”

Environmental Influencers, MicroRNA, and Multiple Sclerosis

“…Unfortunately, the researcher did not find any significant genetic variants that could explain the presence of the disease, suggesting that vitamin D may affect MS by some other means. 66 Agnello et al 67 also did not find a significant association between vitamin D-binding protein (VDBP) and CYP27B1 genetic variants and MS. In addition, Barizzone et al 68 did not find any genetic association between CYP27B1 and 2608 Italian and Belgian MS patients.…”