A new type 1 diabetes susceptibility locus containing the catalase gene (chromosome 11p13) in a Russian population.
BACKGROUND
Oxidative stress is involved in the origin of type 1 diabetes. Low efficiency of the scavenging antioxidant system has been shown to be related to the pathogenesis of the disease. This, therefore suggests that genes encoding catalase and other antioxidant enzymes may implicate in the development of type 1 diabetes.


METHODS
Nine microsatellite markers that cover about 10 megabases around the catalase (CAT) gene on chromosome 11p13 were analyzed using polymerase chain reaction (PCR) and fluorescence-based genotyping on an automatic DNA sequencer. We also evaluated three single-nucleotide polymorphisms (SNP) within genes encoding catalase (T1667T and C(-262)T dimorphism) and ETS homologous factor (EHF) (C255T SNP) using a PCR-restriction fragment-length polymorphism approach. Multipont linkage analysis in 37 affected sibling pairs was performed using GENEHUNTER 2.1. We examined the markers for association with the disease by transmission disequilibrium tests in 57 discordant sibling pairs and by a case-control study in 258 unrelated healthy donors and 247 affected patients.


RESULTS
We obtained close-to-suggestive evidence of linkage to type I diabetes, with the maximum linkage peak between markers D11S907 and D11S2008. Analysis of three SNPs at the CAT and EHF gene located within the region of maximum linkage showed that T1667T and C(-262)T markers of the CAT gene are strongly associated with the disease.


CONCLUSIONS
Our findings support evidence of a new putative type 1 diabetes susceptibility locus on chromosome 11p13 and suggest that the CAT gene may play a role in conferring susceptibility to the disorder in Russian patients.
Chistiakov
D A
DA
Laboratory of Aquatic Ecology, Katholieke Universiteit Leuven, Leuven, Belgium. dimitry.chistiakov@bio.kuleuven.ac.be
Savost'anov
K V
KV
Turakulov
R I
RI
Titovich
E V
EV
Zilberman
L I
LI
Kuraeva
T L
TL
Dedov
I I
II
Nosikov
V V
VV
D000328:Adult; D000483:Alleles; D002374:Catalase / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D004247:DNA / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012426:Russia
D004247:DNA; D002374:Catalase