title: Influence of HLA DQ 2/8 genotypes in predisposing type 1 diabetes in siblings of a Saudi family with paternally inherited chromosomal translocations.
abstract: Type 1 diabetes is one of the most widely studied complex genetic disorders and the genes in human leukocyte antigen (HLA) locus are reported to account approximately 40%-50% of familial aggregation of type 1 diabetes. Genetic markers are helpful in assessing the risk of type 1 diabetes in the general population as well as in close relatives of a patient with type 1 diabetes. The major genetic determinants of this disease are polymorphisms of class II HLA genes encoding DQ and DR. The major susceptibility genes for type 1 diabetes are in the HLA region, and over 90% of patients carry genotypes DR4, DQ8 and/or DR3, DQ2. Absence of the above alleles makes type 1 diabetes very unlikely, especially if the subject carries protective genotypes such as DR2 and/or DQ6. In this brief report of a consanguineous Saudi family, four offsprings inherited one or both of balanced reciprocal translocations from their father. Two offsprings, one with a translocation and the other without, developed type 1 diabetes during early childhood. Both these diabetic children were found to have HLA genotype DQ 2/8, whereas the father and the youngest daughter, both carrying two sets of balanced translocations as well as the protective HLA genotype DQ6, were free of diabetes during several years of observation. This underscores the influence of HLA genotype DQ 2/8 in the susceptibility and DQ6 in the protective effect on type 1 diabetes even in individuals with gross chromosomal abnormalities.
authors.affiliation: Department of Pediatrics, KIMS Hospital and Surgical Center, Cochin-682033, India. mathewpcherian@yahoo.com
authors.forename: Mathew P
authors.initials: MP
authors.lastname: Cherian
mesh_terms: D000293:Adolescent; D018912:Arabs / Q000235:genetics*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012529:Saudi Arabia / Q000453:epidemiology; D014178:Translocation, Genetic / Q000235:genetics*; D055815:Young Adult
chemical_list: D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen