title: A study of promoter and intronic markers of ApoI/Fas gene and the interaction with Fas ligand in relapsing multiple sclerosis.
abstract: We studied the association between multiple sclerosis (MS) and a novel single nucleotide polymorphism (SNP), A/T(735)G/C, localized in intron IV of the ApoI/Fas gene, which is recognized by the restrictase MaeI. Fas-MaeI genotypes were screened in chromosomes of 215 healthy individuals and 312 relapsing MS patients of Spanish extraction. We also analyzed the interaction of this new intragenic marker with others previously associated with MS: class II HLA-DRB1*1501, Fas-MvaI and Fas ligand. The distribution of Fas-MaeI genotypes was in equilibrium in the control cohort, while a significant disequilibrium was observed in the patient group (chi(2) = 16; p = 0.0003). Fas-MaeI genotypes were statistically different in the MS and control groups, but the allele frequencies were not. Sharing of MvaI/MaeI genotypes of the promoter/intron IV region did not differ between patients and controls. We failed to find different frequencies of ApoI/Fas genotypes in the population of MS carriers of the class II HLA-DRB1*1501 allele. The case/control comparative study showed a relative risk (OR close to 1.6) of MS in individuals harboring the T and A alleles of Fas- MaeI and Fas ligand, respectively. In conclusion, our findings suggest a weak association between the intronic marker Fas-MaeI and MS and a relative interaction with Fas ligand in an MS cohort of South Spanish extraction.
authors.affiliation: Servicio de Biología Molecular, Hospital Universitario Virgen Macarena, Avda. Dr. Fedriani s/n, ES-41009 Seville, Spain. lucas@us.es
authors.forename: Miguel
authors.initials: M
authors.lastname: Lucas
authors.forename: María D
authors.initials: MD
authors.lastname: Zayas
authors.forename: Alzenira F
authors.initials: AF
authors.lastname: De Costa
authors.forename: Francisca
authors.initials: F
authors.lastname: Solano
authors.forename: Amal
authors.initials: A
authors.lastname: Chadli
authors.forename: Luminita
authors.initials: L
authors.lastname: Dinca
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
mesh_terms: D000328:Adult; D000409:Alanine / Q000235:genetics; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics* / Q000378:metabolism; D004185:Disability Evaluation; D053222:Fas Ligand Protein; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008075:Lipoproteins, HDL / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008075:Lipoproteins, HDL; D008562:Membrane Glycoproteins; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D000409:Alanine; D005998:Glycine