Identification of 11 novel and common single nucleotide polymorphisms in the interleukin-7 receptor-α gene and their associations with multiple sclerosis (original) (raw)
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IL-7R α polymorphisms in 60 Iranian multiple sclerosis patients
Iranian Journal of Neurology, 2012
Background: Multiple sclerosis (MS), a chronic inflammatory demyelinating disorder with neurodegenerative aspects, is more common among young adults, particularly women. Methods: This molecular study was designed to investigate the IL-7R α chain gene in Iranian MS patients. We studied 60 MS patients, diagnosed based on 2005 R-McDonald criteria and 60 apparently healthy individuals as the control group. DNA was extracted from whole blood cells using MBST/IRAN Extraction kit and all samples were screened for possible sequence variation in three regions including promoter, exon 2 and exon 4 with single strand conformation polymorphism (SSCP). Results: The alterations were confirmed with direct sequencing by ABI 3730XL. Although no mutation was detected in the studied regions, eight single nucleotide polymorphisms (SNPs) consisting of rs71617734 in promoter;
Iranian Journal of Neurology IL-7R α polymorphisms in 60 Iranian multiple sclerosis patients
Iranian Journal of Child Neurology, 2012
Background: Multiple sclerosis (MS), a chronic inflammatory demyelinating disorder with neurodegenerative aspects, is more common among young adults, particularly women. Methods: This molecular study was designed to investigate the IL-7R α chain gene in Iranian MS patients. We studied 60 MS patients, diagnosed based on 2005 R-McDonald criteria and 60 apparently healthy individuals as the control group. DNA was extracted from whole blood cells using MBST/IRAN Extraction kit and all samples were screened for possible sequence variation in three regions including promoter, exon 2 and exon 4 with single strand conformation polymorphism (SSCP). Results: The alterations were confirmed with direct sequencing by ABI 3730XL. Although no mutation was detected in the studied regions, eight single nucleotide polymorphisms (SNPs) consisting of rs71617734 in promoter;
2015
Objective(s): Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) with unknown etiology. Various genetics and environmental factors contribute to the pathogenesis of the disease. The interleukin-7 receptor alpha chain (IL-7Ra) was identified as the first non-major histocompatibility complex (non-MHC) MS susceptibility locus. In this study we are trying to find the association of IL-7Ra gene polymorphisms with MS susceptibility in Eastern Iran. Materials and Methods: A case-control study was performed in two provinces Sistan & Baluchistan and Khorasan with 219 patients and 258 unrelated matched healthy controls, using PCR-RFLP method for four single nucleotide polymorphisms (SNPs) rs7718919, rs11567685, rs11567686 and rs6897932 of IL-7Ra gene. Results: We found a tendency toward association with genotyping analyses in SNP rs7718919 (P=0.048, OR=4.344, and 95% CI=0.892-21.146); also genotype and allele frequency in gender and MS subtype s...
Iranian journal of allergy, asthma, and immunology, 2017
The association of single nucleotide polymorphisms (SNPs) of the IL-7Rα gene with multiple sclerosis (MS) have been documented in various populations. This study aimed to evaluate the genotype distributions of two SNPs, rs6897932 and rs201084372, and the functional association of rs6897932 in relation to IL-7Rα gene expression in a group of Iranian relapsing-remitting MS (RRMS) patients. Genotyping for both SNPs in the IL7Rα gene and relative quantification of mRNA expression for both isoforms of IL-7Rα were performed in 100 RRMS patients and 100 ethnic-matched healthy controls. Higher significant frequencies of the T allele and TT genotype for rs6897932 (C/T) were observed in patients comparing to controls (p=0.006). Higher frequencies of the T allele and the TT and TG genotypes and lower frequencies of the G allele and GG genotypes for rs201084372 (G/A) were found in patients comparing to controls (p<0.0001). A decreased level of mRNA expression for the membrane-bound IL-7Rα ...
Variation in SNPs of the IL7Ra Gene is Associated with Multiple Sclerosis in the Iranian Population
Immunological Investigations, 2011
Interleukin-7 receptor-alpha gene (IL7Ra) is a member of the type I cytokine receptor family located on 5p13 human chromosome. Some evidence associates multiple sclerosis and single nucleotide polymorphisms in the promoter and exonic region of IL7Ra gene. In an attempt to clarify this association, the frequency of 3 SNPs located in the promoter and 1 SNP located in the 6th exon of IL7Ra gene were analyzed in a population of 100 Iranian MS patients as well as 100 controls. Restriction enzyme digestion and a designed mismatch PCR-RFLP strategy were used for the SNP genotyping of our study groups. Considering allele, genotype and haplotype frequencies, no significant association was observed between MS and IL7Ra polymorphisms. Meanwhile, a significant difference was detected between control and primary progressive MS patients considering promoter SNPrs11567685 marker frequency. Also, a significant difference was detected considering exonic SNPrs6897932 for secondary progressive MS patients. Our analysis indicates that GCAC and GTAT haplotypes are less common in SP and PP MS groups, respectively. These differences support the concept that clinical phenotypes may have different etiologies and, therefore, require different therapy strategies.
Advance Biomedical Research, 2014
Background: Multiple sclerosis (MS) is an inflammatory neurodegenerative disease in which the insulating membrane of central nervous system is damaged. The etiology of MS includes both genetic and environmental causes. A Genome-Wide Association Study (GWAS) recognized genetic single nucleotide polymorphisms (SNP) linked with MS predisposition among which immunologically related genes are considerably over signified. The purpose of the present study is to explore the association of rs1520333 C/T polymorphism in the IL7 gene variants with the risk of MS in a subset of Iranian population. Materials and Methods: In this case-control study, 110 cases with MS and 110 controls were contributed. DNA was extracted from blood samples and to amplify the fragment of interest contain rs1520333 SNP, polymerase chain reaction-restriction fragment length polymorphism method was implemented for genotyping of the DNA samples with a specific restriction enzyme (MwoI). SPSS for Windows software (version 18.0; SPSS, Chicago, IL, USA) was used for statistical analysis. Result: We demonstrated the important association between G allele [odds ratio (OR) =1.6614, confidence interval (CI) =1.12-2.47, P = 0.0124] and GG genotype (OR = 7.45, 95% CI = 2.13-25.97, P 0.0016) of the rs1520333 SNP for susceptibility to MS after adjustment for age, and gender. OR adjusted for age, gender, and body mass index has displayed similar outcomes. Conclusion: These results indicate that the rs1520333 SNP is a significant susceptibility gene variant for development of MS in the Iranian population. Nevertheless, functional studies are required to completely elucidate how this SNP contributed to MS pathogenesis.
Nature Genetics, 2007
for the Multiple Sclerosis Genetics Group Multiple sclerosis is a demyelinating neurodegenerative disease with a strong genetic component. Previous genetic risk studies have failed to identify consistently linked regions or genes outside of the major histocompatibility complex on chromosome 6p. We describe allelic association of a polymorphism in the gene encoding the interleukin 7 receptor a chain (IL7R) as a significant risk factor for multiple sclerosis in four independent family-based or case-control data sets (overall P ¼ 2.9 Â 10-7). Further, the likely causal SNP, rs6897932, located within the alternatively spliced exon 6 of IL7R, has a functional effect on gene expression. The SNP influences the amount of soluble and membrane-bound isoforms of the protein by putatively disrupting an exonic splicing silencer.