CTLA4 gene polymorphisms are associated with, and linked to, insulin-dependent diabetes mellitus in a Russian population.
BACKGROUND
The association between the human cytotoxic T lymphocyte-associated antigen-4 (CTLA4) gene and insulin-dependent diabetes mellitus (IDDM) is unclear in populations. We therefore investigated whether the gene conferred susceptibility to IDDM in a Russian population. We studied two polymorphic regions of the CTLA4 gene, the codon 17 dimorphism and the (AT)n microsatellite marker in the 3' untranslated region in 56 discordant sibling pairs and in 33 identical by descent (IBD) affected sibships.


RESULTS
The Alal7 allele of the CTLA4 gene was preferentially transmitted from parents to diabetic offspring (p<0.0001) as shown by the combined transmission/disequlibrium test (TDT) and sib TDT (S-TDT) analysis. A significant difference between diabetic and non-diabetic offspring was also observed for the transmission of alleles 17, 20, and 26 of the dinucleotide microsatellite. Allele 17 was transmitted significantly more frequently to affected offspring than to other children (p=0.0112) whereas alleles 20 and 26 were transmitted preferentially to non-diabetic sibs (p=0.045 and 0.00068 respectively). A nonrandom excess of the Ala17 CTLA4 molecular variant (maximum logarithm of odds score (MLS) of 3.26) and allele 17 of the dinucleotide marker (MLS=3.14) was observed in IBD-affected sibling pairs.


CONCLUSIONS
The CTLA4 gene is strongly associated with, and linked to IDDM in a Russian population.
Chistiakov
D A
DA
INSERM U36-College de France, 75231 Paris Cedex 05, France. dimitry.chistiakov@eudoramail.com
Savost'anov
K V
KV
Nosikov
V V
VV
D000069594:Abatacept; D000293:Adolescent; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005192:Family Health; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D018796:Immunoconjugates; D011110:Polymorphism, Genetic; D012426:Russia
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept