title: Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups.
abstract: Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)n microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P = 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10(-5)), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Marron
authors.forename: L J
authors.initials: LJ
authors.lastname: Raffel
authors.forename: H J
authors.initials: HJ
authors.lastname: Garchon
authors.forename: C O
authors.initials: CO
authors.lastname: Jacob
authors.forename: M
authors.initials: M
authors.lastname: Serrano-Rios
authors.forename: M T
authors.initials: MT
authors.lastname: Martinez Larrad
authors.forename: W P
authors.initials: WP
authors.lastname: Teng
authors.forename: Y
authors.initials: Y
authors.lastname: Park
authors.forename: Z X
authors.initials: ZX
authors.lastname: Zhang
authors.forename: D R
authors.initials: DR
authors.lastname: Goldstein
authors.forename: Y W
authors.initials: YW
authors.lastname: Tao
authors.forename: G
authors.initials: G
authors.lastname: Beaurain
authors.forename: J F
authors.initials: JF
authors.lastname: Bach
authors.forename: H S
authors.initials: HS
authors.lastname: Huang
authors.forename: D F
authors.initials: DF
authors.lastname: Luo
authors.forename: A
authors.initials: A
authors.lastname: Zeidler
authors.forename: J I
authors.initials: JI
authors.lastname: Rotter
authors.forename: M C
authors.initials: MC
authors.lastname: Yang
authors.forename: T
authors.initials: T
authors.lastname: Modilevsky
authors.forename: N K
authors.initials: NK
authors.lastname: Maclaren
authors.forename: J X
authors.initials: JX
authors.lastname: She
mesh_terms: D000069594:Abatacept; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology* / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D006801:Humans; D018796:Immunoconjugates; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept