Evaluation of IDDM8 susceptibility locus in a Russian simplex family data set.
Type 1 diabetes (T1D) susceptibility locus, IDDM8, has been accurately mapped to 200 kilobases at the terminal end of chromosome 6q27. This is within the region which harbours a cluster of three genes encoding proteasome subunit beta 1 (PMSB1), TATA-box binding protein (TBP) and a homologue of mouse programming cell death activator 2 (PDCD2). In this study, we evaluated whether these genes contribute to T1D susceptibility using the transmission disequilibrium test of the data set from 114 affected Russian simplex families. The A allele of the G/A1180 single nucleotide polymorphism (SNP) at the PDCD2 gene, which was significant in its preferential transfer from parents to diabetic children (75 transmissions vs. 47 non-transmissions, chi2=12.85, P corrected=0.0038), was found to be associated with T1D. G/A1180 dimorphism and two other SNPs, C/T771 TBP and G/T(-271) PDCD2, were shown to share three common haplotypes, two of which (A-T-G and A-T-T) have been associated with higher development risk of T1D. The third haplotype (G-T-G) was related to having a lower risk of disease. These findings suggest that the PDCD2 gene is a likely susceptibility gene for T1D within IDDM8. However, it was not possible to exclude the TBP gene from being another putative susceptibility gene in this region.
Chistiakov
Dimitry A
DA
Laboratory of Aquatic Ecology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Seryogin
Yuri A
YA
Turakulov
Rustam I
RI
Savost'anov
Kirill V
KV
Titovich
Elena V
EV
Zilberman
Lyubov' I
LI
Kuraeva
Tamara L
TL
Dedov
Ivan I
II
Nosikov
Valery V
VV
D000293:Adolescent; D000328:Adult; D000483:Alleles; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D012426:Russia