title: Mating in parents of type 1 diabetes families as a function of the HLA DR-DQ haplotype.
abstract: OBJECTIVE
  The Major Histocompatibility Complex (MHC) region on chromosome 6p21 (IDDM1) contributes about half of the familial clustering of type 1 diabetes (T1D). Several studies have revealed that highly polymorphic genes within the MHC may associate with the mating choice. Our study should determine whether a specific mating effect is detectable in T1D families as a function of human leucocyte antigen (HLA) DR-DQ, which could contribute to disease susceptibility.
  
  
  METHODS
  We analysed the parental HLA-DR genotypes in 829 diabetic families. The families derive from the Type 1 Diabetes Genetics Consortium (T1DGC) in addition to those of our own centre and the original UK, US and SCAND diabetic families.
  
  
  RESULTS
  A total of 307 of 829 parental couples (37.0%) were matched for at least one known T1D risk haplotype (DR3 or DR4), which is significantly less than the expected 374.9 (45.2%), derived from population genotype frequencies (p < 0.0009). Parents share less susceptibility haplotypes and rather complement each other as both carry one different risk haplotype (DR3 or DR4). The number of such parental couples was significantly higher than expected (293 vs. 223.4; p < 0.0003). All non-transmitted DR haplotype pairs were also analysed. More often than expected, both parents did not transmit DR1 (94 vs. 59.1; p < 0.003) and DRy (y: not DR1, not DR3, not DR4; 63 vs. 30.3; p < 0.0005). In contrast, the parental non-transmitted pair of haplotypes DR1-DRy was observed to a far lesser extent than expected (26 vs. 84.7; p < 10(-8)). These observations were only made in multiplex families, whereas in simplex families, no deviation from the expected frequencies was observed.
  
  
  CONCLUSIONS
  Our data are consistent with the conclusion that genes in the HLA region may influence the mating choice in parents of T1D patients, thus contributing to familial clustering of T1D in multiplex families. This may indicate a different parental background of multiplex compared with simplex T1D families.
authors.affiliation: Division of Endocrinology and Department of Immunohaematology, University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Kahles
authors.forename: O
authors.initials: O
authors.lastname: Kordonouri
authors.forename: E
authors.initials: E
authors.lastname: Ramos Lopez
authors.forename: M
authors.initials: M
authors.lastname: Walter
authors.forename: S
authors.initials: S
authors.lastname: Rosinger
authors.forename: B O
authors.initials: BO
authors.lastname: Boehm
authors.forename: K
authors.initials: K
authors.lastname: Badenhoop
authors.forename: C
authors.initials: C
authors.lastname: Seidl
authors.forename: A
authors.initials: A
authors.lastname: Ziegler
mesh_terms: D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D012725:Sexual Behavior / Q000502:physiology*; D013997:Time Factors
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens