CD6 gene polymorphism rs17824933 is associated with multiple sclerosis in Indian population

Abstract

Background:Multiple sclerosis (MS) prevalence has increased worldwide. The known genetic association for MS in the west has not been studied in detail in nonwhite populations and particularly Indians.Objective:The objective of this study was to evaluate some known genetic variations outside the major histocompatibility complex (MHC) region associated with MS in patients of Indian origin.Materials and Methods:We investigated 10 gene-associated single nucleotide polymorphisms (SNP's) outside the MHC region in 300 patients and 720 unrelated controls. Genotyping was performed on an ABI7500 real-time polymerase chain reaction genotyping platform using predesigned TaqMan SNP genotyping assays.Results:CD6 gene associated SNP (rs17824933) showed significant association with MS (P = 4.2 × 10−5, odds ratio [OR] = 2.24, confidence interval (CI) = 1.51–3.33). A modest association was also noted for TMEM39A rs1132200 (P = 0.023, OR = 1.41, CI = 1.05–1.91) and IL2RA rs2104286 (P = 0.04, OR = 1.3, CI = 1.006–1.67). In the remaining SNPs, the allele frequencies were overexpressed in patients when compared to healthy controls.Conclusion:Our data illustrate the similarity in risk association between Indian and European populations for MS.

Preliminary Study on the Role of TMEM39A Gene in Multiple Sclerosis

“…We did not find an association of rs1132200 with MS susceptibility. In contrast to our findings, GWAS conducted by IMSGC (International Multiple Sclerosis Genetics C 2010) as well as replication studies performed on a Spanish population (Varade et al 2012) and Indian population (D'Cunha et al 2016) identified polymorphism rs1132200G>A of TMEM39A as the potential risk factor for MS with the common allele (G allele) increasing predisposition. According to Salanti et al (Salanti et al 2005), in the presence of an association, Hardy–Weinberg equilibrium in cases does not have to be maintained.…”

Soluble CD72, is a T-cell activator probably via binding to CD6 in homeostasis and autoimmunity

“…For example, CD6 and its ligand ALCAM (CD166) are considered to be risk factors for the neuro-autoimmune disease multiple sclerosis (MS). It is possible that these two molecules might contribute to pathogenesis by enhancing active T-cell migration across the brain barrier ( 22 , 23 ). Knockout of CD6 in MS mice model (EAE) could decrease the infiltration of inflammatory T cells into the nervous system and thereby protect from developing the disease ( 24 ).…”

Multiple sclerosis in India

“…[ 29 ]Pandit et al evaluated 109 European-associated variants in a total of 270 patients with MS and 555 controls and showed that two-third of variants overlapped suggesting similarity in etiology irrespective of ethnicity[ 30 ]as well as human leukocyte antigen (HLA) (DRB1 × 15:01 and DRB1 × 03 alleles) similarity[ 31 ]and also showed CD6 gene polymorphism rs17824933 as seen in European population. [ 32 ]Zahoor et al evaluated Ile587Val polymorphism of the EIF2B5 gene in MS in Kashmir and did not find any polymorphism[ 33 ]and also reported the clinical profile of 14 patients of MS from Kashmir. [ 34 ]…”