Evidence for a new Graves disease susceptibility locus at chromosome 18q21

Am J Hum Genet. 2000 May;66(5):1710-4. doi: 10.1086/302908. Epub 2000 Apr 3.

Abstract

Graves disease (GD) is a common autoimmune thyroid disorder that is inherited as a complex multigenic trait. By using a single microsatellite marker at each locus, we screened the type 1 diabetes loci IDDM4, IDDM5, IDDM6, IDDM8, and IDDM10 and the fucosyltransferase-2 locus for linkage in sib pairs with GD. This showed a two-point nonparametric linkage (NPL) score of 1.57 (P=.06) at the IDDM6 marker D18S41, but NPL scores were <1.0 at the other five loci. Thus, the investigation of the IDDM6 locus was extended by genotyping 11 microsatellite markers spanning 48 cM across chromosome 18q12-q22 in 81 sib pairs affected with autoimmune thyroid disease (AITD). Multipoint analysis, designating all AITD sib pairs as affected, showed a peak NPL score of 3.46 (P=.0003), at the marker D18S487. Designation of only GD cases as affected (74 sib pairs) showed a peak NPL score of 3.09 (P=.001). Linkage to this region has been demonstrated in type 1 diabetes (IDDM6), rheumatoid arthritis, and systemic lupus erythematosus, which suggests that this locus may have a role in several forms of autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Chromosome Mapping
  • Chromosomes, Human, Pair 18 / genetics*
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / genetics
  • Female
  • Fucosyltransferases / genetics
  • Galactoside 2-alpha-L-fucosyltransferase
  • Genetic Heterogeneity
  • Genetic Linkage / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Graves Disease / genetics*
  • Humans
  • Male
  • Matched-Pair Analysis
  • Microsatellite Repeats / genetics
  • Models, Genetic
  • Nuclear Family
  • Phenotype
  • Statistics, Nonparametric
  • Thyroiditis, Autoimmune / genetics
  • White People / genetics

Substances

  • Fucosyltransferases