TY - JOUR
T1 - Influence of the LILRA3 Deletion on Multiple Sclerosis Risk:
T2 - Original Data and Meta-Analysis
AU - Ortiz, Miguel A.
AU - Nunez, Concepcion
AU - Ordonez, David
AU - Alvarez-Cermeno, Jose C.
AU - Martinez-Rodriguez, Jose E.
AU - Sanchez, Antonio J.
AU - Arroyo, Rafael
AU - Izquierdo, Guillermo
AU - Malhotra, Sunny
AU - Montalban, Xavier
AU - Garcia-Merino, Antonio
AU - Munteis, Elvira
AU - Alcina, Antonio
AU - Comabella, Manuel
AU - Matesanz, Fuencisla
AU - Villar, Luisa M.
AU - Urcelay, Elena
PY - 2015/8/14
Y1 - 2015/8/14
N2 - 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.
AB - 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.
KW - Immunoglobulin-like receptors
KW - Ilt6 gene
KW - Association
KW - Susceptibility
KW - Organization
KW - Protein
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=uab_pure&SrcAuth=WosAPI&KeyUT=WOS:000359493600026&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1371/journal.pone.0134414
DO - 10.1371/journal.pone.0134414
M3 - Article
C2 - 26274821
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 8
M1 - e0134414
ER -