The cytotoxic T lymphocyte antigen 4 (CTLA4) acts as a potent negative regulator of T-cell response, and has been suggested as a pivotal candidate gene for autoimmune disorders such as Graves' disease, type 1 diabetes and autoimmune hypothyroidism, among others. Several single-nucleotide polymorphisms (SNPs) have been proposed as the susceptibility variants, or to be in strong linkage disequilibrium (LD) with the variant. Nevertheless, contradictory results have been found, which may be due to lack of knowledge of the genetic structure of CTLA4 and its geographic variation. We have typed 17 SNPs throughout the CTLA4 gene region in order to analyze the haplotype diversity and LD structure in a worldwide population set (1262 individuals from 44 populations) to understand the variation pattern of the region. Allele and haplotype frequency differentiation between populations is consistent with genomewide averages and points to a lack of strong population-specific selection pressures. LD is high and its pattern is not significantly different within or between continents. However, haplotype composition is significantly different between geographical groups. A continent-specific set of haplotype tagging SNPs has been designed to be used for future association studies. These are portable among populations, although their efficiency might vary depending on the population haplotype spectrum.

CTLA4 gene, Haplotype, Linkage disequilibrium, Population diversity, Tag-SNP,
Genes and Immunity
Centre for Rotterdam Cultural Sociology (CROCUS)

Ramírez-Soriano, A, Lao Grueso, O, Soldevila, M, Calafell, F, Bertranpetit, J, & Comas, D. (2005). Haplotype tagging efficiency in worldwide populations in CTLA4 gene. Genes and Immunity, 6(8), 646–657. doi:10.1038/sj.gene.6364251