Hepcidin (rs10421768), Transferrin (rs3811647, rs1049296) and Transferrin Receptor 2 (rs7385804) Gene Polymorphism Might Be Associated with the Origin of Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system in which there is a multifocal damage to the nerve tissue. Additionally, the literature emphasizes the excessive accumulation of iron in the central nervous system of patients, which is negatively correlated with their psychophysical fitness. Iron metabolism genes polymorphisms may modulate iron deposition in the body and thus affect the clinical course of MS. We aimed to assess the frequency of HAMP, TFR2, and TF polymorphisms in MS patients and their impact on the clinical course of the disease. The studied polymorphisms were identified by the Real-Time PCR using TaqMan technology. Neurological assessment by means of EDSS scale was conducted. This cross-sectional study included 176 patients, with the mean age of onset of symptoms at 30.6 years. The frequency of alleles of the studied polymorphisms was as follows: (a) HAMP rs10421768: A 75.9% (n = 267), G 24.1% (n = 65), (b) TF rs1049296: C 89.2% (n = 314), T 10.8% (n = 38), (c) TF rs3811647: A 39.8% (n = 140), G 60.2% (n = 212), (d) TFR2 rs7385804: A 59.1% (n = 59.1%), C 40.9% (n = 144). In the codominant inheritance model of TF rs1049269, it was shown that people with the CT genotype scored statistically significantly lower points in the EDSS scale at the time of diagnosis than those with the CC genotype (CC Me = 1.5, CT Me = 1.0 p = 0.0236). In the recessive model of TF inheritance rs3811647, it was noticed that the primary relapses were significantly more frequent in patients with at least one G allele compared with those with the AA genotype (AG + GG = 81.2%, AA = 18.8%, p = 0.0354). In the overdominant model rs7385804 TFR2, it was shown that among patients with the AA genotype, multiple sclerosis occurs significantly more often in relatives in a straight line compared with people with the AC and CC genotypes (AA = 100.0%, AC + CC = 0.0%, p = 0.0437). We concluded that the studied polymorphisms might affect the clinical course of MS.

Rs205764 and rs547311 in linc00513 may influence treatment responses in multiple sclerosis patients: A pharmacogenomics Egyptian study

“…These finding appear to be partially consistent, in terms of patient disability, with the study reporting rs205764 and rs547311 as novel regulators of IFN signaling ( 12 ), where the resulting overexpression of linc00513 has been associated with a higher IFN score for SLE patients. Moreover, several other variants have previously been associated with differences in EDSS for MS patients, including rs17445836 in interferon regulatory factor-8 gene ( 23 ), rs3087456 and rs4774 in class-II trans-activator gene ( 24 ), rs1049269 in transferrin gene ( 25 ), and rs1494555 in interleukin-7 receptor gene ( 26 ).…”

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

“…GO and REACTOME pathway enrichment analyses were used to explore the molecular mechanisms of the genes involved in the occurrence and development of MS. It is well known that the pathways include immune system [55], TCR signaling [56], cytokine signaling in immune system [57], degradation of the extracellular matrix [58], extracellular matrix organization [58], metabolism of lipids [59] and metabolism [60] plays an important role only in MS. CCL18 [61], FCRL3 [62], EOMES (eomesodermin) [63], CCR2 [64], IL2RB [65], CCL4 [66], FASLG (Fas ligand) [67], CD24 [68], IKZF3 [69], CD2 [70], CD28 [71], IL7R [72], HLA-DRB5 [73], ICOS (inducible T cell costimulator) [74], CCL5 [75], CTLA4 [76], IRF4 [77], C6 [78], NCR1 [79], CHIT1 [80], CD52 [81], CD163 [82], HGF (hepatocyte growth factor) [83], DIO3 [84], SIGLEC1 [85], TTR (transthyretin) [86], IL9 [87], VEGFA (vascular endothelial growth factor A) [88], CR2 [89], ANGPTL4 [90], CHI3L1 [91], MAG (myelin associated glycoprotein) [92], CNP (2’,3’-cyclic nucleotide 3’ phosphodiesterase) [93], CMTM5 [94], SEMA4D [95], NGFR (nerve growth factor receptor) [96], TF (transferrin) [97], MYRF (myelin regulatory factor) [98], MOG (myelin oligodendrocyte glycoprotein) [99], ADAMTS4 [100], BMP2 [101], HTRA1 [102], PNPLA3 [103], DYSF (dysferlin) [104], NINJ2 [105], LRP2 [106], ADAMTS14 [107] and DHCR7 [108] might play an important role in regulating the occurrence and development of MS. The expression of CCL18 [109], SLAMF7 [110], GPR174 [111], CCR4 [112], POU4F2 [113].…”

Common Single Nucleotide Polymorphism of TMPRSS6, an Iron Regulation Gene, Associated with Variable Red Blood Cell Indices in Deletional α-Globin Genotypes

“…Several polymorphisms associate with iron homeostasis in human, including p.C282Y (c.845 G>A; rs1800562) and p.H63D (c.187 C>G; rs1799945) of human hemochromatosis protein ( HFE ), the SNP -8CG and -98GC of ferroportin ( FPN1 ), SNP c.−582A>G; rs10421768 on the hepcidin anti-microbial peptide ( HAMP ) promoter region, p. P570S (C>T; rs1049296) of transferrin ( TF ) and p.V736A (T>C; rs855791) of TMPRSS6 [ 7 , 20 , 21 , 22 , 23 , 24 ]. TMPRSS6 is a type of trans-membrane serine protease mainly involved in iron homeostasis resulting in resistance to IRIDA disorder.…”