Abstract
BackgroundMultiple sclerosis (MS) is a neurodegenerative, autoimmune disease of the central nervous system. Genome-wide association studies (GWAS) have identified over hundred polymorphisms with modest individual effects in MS susceptibility and they have confirmed the main individual effect of the Major Histocompatibility Complex. Additional risk loci with immunologically relevant genes were found significantly overrepresented. Nonetheless, it is accepted that most of the genetic architecture underlying susceptibility to the disease remains to be defined. Candidate association studies of the leukocyte immunoglobulin-like receptor LILRA3 gene in MS have been repeatedly reported with inconsistent results.ObjectivesIn an attempt to shed some light on these controversial findings, a combined analysis was performed including the previously published datasets and three newly genotyped cohorts. Both wild-type and deleted LILRA3 alleles were discriminated in a single-tube PCR amplification and the resulting products were visualized by their different electrophoretic mobilities.Results and ConclusionOverall, this meta-analysis involved 3200 MS patients and 3069 matched healthy controls and it did not evidence significant association of the LILRA3 deletion [carriers of LILRA3 deletion: p = 0.25, OR (95% CI) = 1.07 (0.95–1.19)], even after stratification by gender and the HLA-DRB1*15:01 risk allele.
Highlights
Multiple sclerosis (MS), a disease of the central nervous system involving chronic inflammation, axonal damage and demyelination, is likely caused by the interplay of genetic and environmental risk factors
Meta-analysis across these published datasets yielded a statistically significant effect in carriers of the LILRA3 deletion [p = 0.03; odds ratios (OR) = 1.19 (1.02–1.40)], with modest evidence of heterogeneity (I2 = 25%)
The greatest advances in the study of this genetic component have been achieved through genome-wide association studies (GWAS), which analyze thousands of patients and ethnically matched controls searching for evidences to explain MS pathogenesis
Summary
Multiple sclerosis (MS), a disease of the central nervous system involving chronic inflammation, axonal damage and demyelination, is likely caused by the interplay of genetic and environmental risk factors. Members of the LILR gene family map to the leukocyte receptor complex on chromosome 19q13.4, a region that encodes at least 24 members of the immunoglobulin superfamily [5]. GWAS benefit of a high throughput technology based on genotyping a growing number of single-nucleotide polymorphisms (SNPs), even over a million. This is a limited strategy to detect any other kind of genetic variants such as deletions, unless they show high linkage disequilibrium with a SNP. Genome-wide association studies (GWAS) have identified over hundred polymorphisms with modest individual effects in MS susceptibility and they have confirmed the main individual effect of the Major Histocompatibility Complex. Candidate association studies of the leukocyte immunoglobulin-like receptor LILRA3 gene in MS have been repeatedly reported with inconsistent results
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
