title: Hexose-6-phosphate dehydrogenase: a new risk gene for multiple sclerosis.
abstract: A recent genome-wide association study (GWAS) performed by the The Wellcome Trust Case-Control Consortium based on 12 374 nonsynonymous single-nucleotide polymorphisms (SNPs) provided evidence for several genes involved in multiple sclerosis (MS) susceptibility. In this study, we aimed at verifying the association of 19 SNPs with MS, with P-values < or =0.005, in an independent cohort of 732 patients and 974 controls, all Caucasian from the South of Spain. We observed an association of the rs17368528 polymorphism with MS (P=0.04, odds ratio (OR)=0.801, 95% confidence interval (CI)=0.648-0.990). The association of this polymorphism with MS was further validated in an independent set of 1318 patients from the Canadian Collaborative Project (P=0.04, OR=0.838, 95% CI=0.716-0.964). This marker is located on chromosome 1p36.22, which is 1 Mb away from the MS-associated kinesin motor protein KIF1B, although linkage disequilibrium was not observed between these two markers. The rs17368528 SNP results in an amino-acid substitution (proline to leucine) in the fifth exon of the hexose-6-phosphate dehydrogenase (H6PD) gene, in which some variants have been reported to attenuate or abolish H6PD activity, in individuals with cortisone reductase deficiency. This study corroborates the association of one locus determined by GWAS and points to H6PD as a new candidate gene for MS.
authors: Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas, Granada, Spain.
authors: Antonio
authors: A
authors: Alcina
authors: Sreeram V
authors: SV
authors: Ramagopalan
authors: Oscar
authors: O
authors: Fernández
authors: Antonio
authors: A
authors: Catalá-Rabasa
authors: María
authors: M
authors: Fedetz
authors: Dorothy
authors: D
authors: Ndagire
authors: Laura
authors: L
authors: Leyva
authors: Carmen
authors: C
authors: Arnal
authors: Concepción
authors: C
authors: Delgado
authors: Miguel
authors: M
authors: Lucas
authors: Guillermo
authors: G
authors: Izquierdo
authors: George C
authors: GC
authors: Ebers
authors: Fuencisla
authors: F
authors: Matesanz
mesh_terms: D000328:Adult; D002170:Canada; D002237:Carbohydrate Dehydrogenases / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000201:enzymology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D013030:Spain; D006113:United Kingdom
chemical_list: D002237:Carbohydrate Dehydrogenases; C020552:galactose-6-phosphate dehydrogenase