title: Evaluation of IDDM8 susceptibility locus in a Russian simplex family data set.
abstract: 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.
authors.affiliation: Laboratory of Aquatic Ecology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
authors.forename: Dimitry A
authors.initials: DA
authors.lastname: Chistiakov
authors.forename: Yuri A
authors.initials: YA
authors.lastname: Seryogin
authors.forename: Rustam I
authors.initials: RI
authors.lastname: Turakulov
authors.forename: Kirill V
authors.initials: KV
authors.lastname: Savost'anov
authors.forename: Elena V
authors.initials: EV
authors.lastname: Titovich
authors.forename: Lyubov' I
authors.initials: LI
authors.lastname: Zilberman
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Kuraeva
authors.forename: Ivan I
authors.initials: II
authors.lastname: Dedov
authors.forename: Valery V
authors.initials: VV
authors.lastname: Nosikov
mesh_terms: 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