Analysis of candidate genes for susceptibility to type I diabetes: a case-control and family-association study of genes on chromosome 2q31-35.
Recent genome searches suggest a putative linkage of many loci to susceptibility to type I diabetes. The chromosome 2q31-35 region is reported to be linked to susceptibility to type I diabetes and is thought to contain several diabetes susceptibility loci. These candidate genes include the HOXD gene cluster, BETA2, CTLA4, CD28, IGFBP2, and IGFBP5. Association studies in populations and families are required to confirm and/or identify the actual susceptibility loci. We hereby report several previously unknown DNA polymorphisms for HOXD8, BETA2, and IGFBP5, which we have used along with previously known polymorphisms of HOXD8 and CTLA4 to test whether these candidate loci are the susceptibility genes on chromosome 2q31-35. Using a case-control design with a subsequent family-association approach to confirm associations, we find no evidence that these candidate genes are associated with susceptibility to type I diabetes.
Owerbach
D
D
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA. davido@mbcr.bcm.tmc.edu
Naya
F J
FJ
Tsai
M J
MJ
Allander
S V
SV
Powell
D R
DR
Gabbay
K H
KH
D000483:Alleles; D051792:Basic Helix-Loop-Helix Proteins; D018106:CD28 Antigens / Q000235:genetics; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005190:Family; D005787:Gene Frequency; D008040:Genetic Linkage; D006684:HLA-DR Antigens / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D018106:CD28 Antigens; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; D018398:Homeodomain Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D018975:Insulin-Like Growth Factor Binding Protein 5; D015534:Trans-Activators; D014157:Transcription Factors; C093970:NEUROD1 protein, human; C075279:HOXD8 protein, human