Influence of the LILRA3 Deletion on Multiple Sclerosis Risk: Original Data and Meta-Analysis.
BACKGROUND
Multiple 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.


OBJECTIVE
In 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.


CONCLUSIONS
Overall, 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.
Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain.
Miguel A
MA
Ortiz
Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain.
Concepción
C
Núñez
Immunogenetics & Histocompatibility, Instituto de Investigación Sanitaria Puerta de Hierro, Majadahonda, Madrid, Spain.
David
D
Ordóñez
Departments of Immunology and Neurology, Multiple Sclerosis Unit, Hospital Ramon y Cajal, (IRYCIS), Madrid, Spain.
José C
JC
Alvarez-Cermeño
Neurology, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
José E
JE
Martínez-Rodriguez
Neuroimmunology, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain.
Antonio J
AJ
Sánchez
Multiple Sclerosis Unit, Neurology Department. Hospital Clínico S. Carlos, Instituto de Investigación Sanitaria S. Carlos (IdISSC), Madrid, Spain.
Rafael
R
Arroyo
Multiple Sclerosis Unit, Hospital Virgen Macarena, Sevilla, Spain.
Guillermo
G
Izquierdo
Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Sunny
S
Malhotra
Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Xavier
X
Montalban
Neuroimmunology, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain.
Antonio
A
García-Merino
Neurology, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Elvira
E
Munteis
Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina "López Neyra", Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), Granada, Spain.
Antonio
A
Alcina
Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Manuel
M
Comabella
Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina "López Neyra", Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), Granada, Spain.
Fuencisla
F
Matesanz
Departments of Immunology and Neurology, Multiple Sclerosis Unit, Hospital Ramon y Cajal, (IRYCIS), Madrid, Spain.
Luisa M
LM
Villar
Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain.
Elena
E
Urcelay
D004843:Epistasis, Genetic; D017353:Gene Deletion; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D044465:White People / Q000331:legislation & jurisprudence
D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; C530062:LILRA3 protein, human; D011971:Receptors, Immunologic