Evaluation of the influence of single-nucleotide polymorphisms of vitamin D receptor (rs2228570), BDNF (rs6265), and NMDA (rs4880213) genes on gene expression in different tissues

Abstract

Background. Questions regarding the association of individual and combined gene variations and mutations with thyroid disease and nervous system disorders remain insufficiently researched and require further study to facilitate early diagnosis of nervous system damage on the background of thyroid pathology, disease prognosis, and timely treatment and prevention. An important issue is the identification of the influence of individual polymorphisms in these genes on the functional activity of cells, including gene expression. Currently, gene expression genetics largely depends on the identification of expression quantitative trait loci (eQTL), which are the links between gene expression and genotype at a locus. The purpose of the study was to search for eQTL in single nucleotide polymorphisms (SNPs) of the BDNF gene (rs6265), VDR gene (rs2228570), and NMDA gene (rs4880213). The results were presented as nominal p-values for each SNP of the BDNF, VDR, and NMDA genes. Materials and methods. We use publicly available databases (QTLbase: http://www.mulinlab.org/qtlbase/index.html, GTExPortal: https://gtexportal.org). Results. Using the QTLbase, we identified statistically significant (p≤0.05) associations of rs6265 with the expression of 17 genes (BDNF-AS, BDNF, LDHC, AC104563.1, BBOX1, SPTY2D1OS, YWHABP2, LINC00678, LIN7C, GTF2H1, METTL15, IMMP1L, KIF18A, HPS5, NAV2, LGR4, CCDC34) in various tissues. For rs4880213, we found a significant association with the expression levels of 49 genes (ARRDC1-AS1, TPRN, SSNA1, SAPCD2, UAP1L1, NPDC1, MAN1B1, PTGDS, SNHG7, NDOR1, TRAF2, PHPT1, EGFL7, EHMT1, RNF208, PNPLA7, LCNL1, DPP7, LCN12, STPG3, CCDC183-AS1, ABCA2, RNF224, ENTPD2, PAXX, CLIC3, C9orf163, LCN15, MAN1B1-DT, FAM166A, FAM166A, LRRC26, STPG3-AS1, AGPAT2, ANAPC2, DPH7, ZMYND19, NSMF, MRPL41, EXD3, TUBB4B, NELFB, ARRDC1, EDF1, FBXW5, DIPK1B, MAMDC4, RABL6, TMEM141, TMEM203) in 16 different tissues. Additionally, we identified statistically significant (p ≤ 0.05) associations of rs2228570 with the expression of 29 genes (ASB8, TMEM106C, KANSL2, DDX23, CCNT1, HDAC7, RPAP3, PFKM, SENP1, RND1, PCED1B, AC004466.1, AMIGO2, ZNF641, ENDOU, RAPGEF3, VDR, AC004241.1, AC004801.2, AC121338.1, LINC02354, SNORA2A, LINC02416, AC074029.3, AC004241.5, AC008083.3, COL2A1, CCDC184, SLC48A1) in 17 different tissues. Conclusions. Single nucleotide polymorphisms of the BDNF (rs6265), VDR (rs2228570), and NMDA genes (rs4880213) affect gene expression in various cells and tissues. The use of this extensive eQTL catalog provides an important resource for understanding the molecular basis of common genetic diseases.