Association of human leukocyte antigen-DRB haplotype in multiple sclerosis population of Khuzestan, Iran

Abstract

Background: One of the demyelinating and inflammatory diseases of the central nervous system (CNS) is multiple sclerosis (MS). Though pathogenesis of MS is still unknown, both genetic and environmental factors are involved. The human leukocyte antigen (HLA) class-II alleles including HLA-DRB5*01, DQB1*0602, DRB1*1501, and DQA1*0102 may have remarkable effect in MS risk although it is controversial in studies. As there is no data with respect to the HLA-DRB1*1501-DRB5*01 correlation with MS in Khuzestan Province, Iran, the goal of the survey was to investigate the association of this haplotype with MS in this population.
 Methods: The study focused on DRB5*01-DRB1*1501 haplotype association with MS in 200 patients and 200 healthy individuals. Typing of HLA was carried out by polymerase chain reaction (PCR) amplification with sequence-specific primers (SSP) method. SPSS software was used for the statistical analyses.
 Results: No association between DRB5*01+-DRB1*1501+ and MS was found (P = 0.156). Distribution of DRB1*1501+-DRB5*01- (carrying DRB1*1501+ but not DRB5*01-) and DRB1*1501--DRB5*01- haplotypes was statistically different between patients and controls (29.73% vs. 11.81%, P < 0.001) and (42.16% vs. 68.50%, P < 0.001), respectively. However, DRB1*1501--DRB5*01+ revealed no association with MS (15.13% vs. 11.81%, P = 0.403). HLA-DRB1*1501--DRB5*01+ was significantly more frequent among female 
 patients with MS (16.19% vs. 6.12%, P = 0.019) and Persian group (17.11% vs. 5.79%, P = 0.027). Positive correlation of HLA-DRB1*1501+-DRB5*01- haplotype with the expanded disability status scale (EDSS) steps from 5 to 10 was observed (62.50% vs. 25.76%, P = 0.026). Moreover, no meaningful association was shown among the haplotypes with EDSS, course of MS, ethnicity, and gender.
 Conclusion: Our findings suggest that DRB1*1501+-DRB5*01- and DRB1*1501--DRB5*01- haplotypes may have positive association with MS risk. Also, this survey indicates that HLA-DRB1*1501--DRB5*01+ is involved in susceptibility of the disease among women and Persians. DRB1*1501+-DRB5*01- genotype frequency may have a key role in MS developing.

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].…”