title: CD1 gene polymorphisms and phenotypic variability in X-linked adrenoleukodystrophy.
abstract: X-linked adrenoleukodystrophy (X-ALD) is characterized by marked phenotypic variation ranging from adrenomyeloneuropathy (AMN) to childhood cerebral ALD (CCALD). X-ALD is caused by mutations in the ABCD1 gene, but no genotype-phenotype correlation has been established so far and modifier gene variants are suspected to modulate phenotypes. Specific classes of lipids, enriched in very long-chain fatty acids that accumulate in plasma and tissues from X-ALD patients are suspected to be involved in the neuroinflammatory process of CCALD. CD1 proteins are lipid- antigen presenting molecules encoded by five CD1 genes in human (CD1A-E). Association studies with 23 tag SNPs covering the CD1 locus was performed in 52 patients with AMN and 87 patients with CCALD. The minor allele of rs973742 located 4-kb downstream from CD1D was significantly more frequent in AMN patients (χ² = 7.6; P = 0.006). However, this association was no longer significant after Bonferroni correction for multiple testing. The other polymorphisms of the CD1 locus did not reveal significant association. Further analysis of other CD1D polymorphisms did not detect stronger association with X-ALD phenotypes. Although the association with rs973742 warrants further investigations, these results indicate that the genetic variants of CD1 genes do not contribute markedly to the phenotypic variance of X-ALD.
authors.affiliation: UMR 745, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. mathieu.barbier@inserm.fr
authors.forename: Mathieu
authors.initials: M
authors.lastname: Barbier
authors.forename: Audrey
authors.initials: A
authors.lastname: Sabbagh
authors.forename: Edwige
authors.initials: E
authors.lastname: Kasper
authors.forename: Muriel
authors.initials: M
authors.lastname: Asheuer
authors.forename: Ornella
authors.initials: O
authors.lastname: Ahouansou
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pribill
authors.forename: Sonja
authors.initials: S
authors.lastname: Forss-Petter
authors.forename: Michel
authors.initials: M
authors.lastname: Vidaud
authors.forename: Johannes
authors.initials: J
authors.lastname: Berger
authors.forename: Patrick
authors.initials: P
authors.lastname: Aubourg
mesh_terms: D000326:Adrenoleukodystrophy / Q000235:genetics* / Q000473:pathology*; D000483:Alleles; D018949:Antigens, CD1 / Q000235:genetics*; D055610:Antigens, CD1d / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; C419394:CD1b antigen