Association of CTLA4 but not ICOS polymorphisms with type 1 diabetes in two populations with different disease rates.
Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and inducible T-cell co-stimulator (ICOS) genes are important mediators of T-cell activation in autoimmune diseases. The aim of the current study was to assess the impact of CTLA-4 and ICOS genes on the susceptibility to type 1 diabetes among two populations with different disease incidence rates. Three single nucleotide polymorphisms (SNPs) within the CTLA-4 region (+49A/G, CT60A/G, CTBC217_1C/T) and two SNPs within the ICOS region (CTIC154_1 C/T, CTIC159 C/G) were genotyped in 955 control subjects and 574 diabetic patients of Estonian and Finnish descent. The current study confirms the involvement of the CTLA-4 but not the ICOS gene in susceptibility to type 1 diabetes. However, the risk alleles and the defined main risk haplotype were more common in the Finnish controls compared with the Estonians, indicating that this gene locus might also be one of the contributing factors to the higher disease incidence in Finland.
Douroudis
Konstantinos
K
Immunology Group, IGMP, University of Tartu, Tartu, Estonia.
Laine
Antti-Pekka
AP
Heinonen
Mirkka
M
Hermann
Robert
R
Lipponen
Kati
K
Veijola
Riitta
R
Simell
Olli
O
Knip
Mikael
M
Uibo
Raivo
R
Ilonen
Jorma
J
Kisand
Kalle
K
D000293:Adolescent; D000328:Adult; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D060908:CTLA-4 Antigen; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D004957:Estonia / Q000453:epidemiology; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D060889:Inducible T-Cell Co-Stimulator Protein; D015810:Linkage Disequilibrium; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein