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Analysis of HLA haplotypes in families with type 1 diabetes mellitus in La Réunion island. 1996

J P Feugeas, and P Tortosa, and S Dulay, and I Augustin-Pascalis, and D Charron, and R Krishnamoorthy, and H Caillens, and C Montchamp-Moreau
Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint-Louis, Paris, France.

To analyse HLA and insulin-dependent diabetes mellitus (IDDM) association in the ethnically mixed population of La Réunion island, we carried out a family study on 70 diabetic subjects. HLA-DQA1, -DQB1 and -DRB1 typing was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), completed by PCR-sequence-specific oligonucleotide (SSO) and PCR-sequence-specific priming (SSP). Haplotype-relative risks (HRR) were determined with the non-transmitted parental haplotypes as controls, and relative risks (RR) were calculated with a classical case-control study. The most significant risks were found for the cis and trans combinations between DQA1*03 or *0501 (Arg52+) and DQB1*02 or *0302 (Asp57-) alleles, suggesting a direct role for the HLA-DQ heterodimer in IDDM susceptibility. Interestingly, due to the mixed origin of the population, the trans-encoded DQ molecules in the (DR3)-DQA1*0501-DQB1*02/(DR4)-DQA1*03-DQB1*0302 subjects were also found cis-encoded in patients with the (DR7 or 9)-DQA1*03-DQB1*02 haplotype and in a patient with the rare (DR11)-DQA1*0501-DQB1*0302 haplotype. A relative predispositional effect (RPE) analysis gave significant haplotype-IDDM+ associations in the following order: (DR3)-DQA1*0501-DQB1*02 > (DR4)-DQA1*03-DQB1*0302 > (DR9)-DQA1*03- DQB*02 > (DR7)-DQA1*03-DQB1*02 > (DR2)-DQA1*01-DQB1*0502. No protective effect remained significant once the susceptible haplotypes were removed. A stratification study showed a stronger influence of the DQ genes than DRB1 alleles within the DR7 haplotypes. On the other hand, IDDM subjects with only one susceptible haplotype had inherited this haplotype more often from their father than from their mother. This paternal effect could be related to the greater risk of IDDM in offspring of diabetic fathers than the risk in offspring of diabetic mothers.

UI MeSH Term Description Entries
D008297 Male Males
D003922 Diabetes Mellitus, Type 1 A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence. Diabetes Mellitus, Brittle,Diabetes Mellitus, Insulin-Dependent,Diabetes Mellitus, Juvenile-Onset,Diabetes Mellitus, Ketosis-Prone,Diabetes Mellitus, Sudden-Onset,Diabetes, Autoimmune,IDDM,Autoimmune Diabetes,Diabetes Mellitus, Insulin-Dependent, 1,Diabetes Mellitus, Type I,Insulin-Dependent Diabetes Mellitus 1,Juvenile-Onset Diabetes,Type 1 Diabetes,Type 1 Diabetes Mellitus,Brittle Diabetes Mellitus,Diabetes Mellitus, Insulin Dependent,Diabetes Mellitus, Juvenile Onset,Diabetes Mellitus, Ketosis Prone,Diabetes Mellitus, Sudden Onset,Diabetes, Juvenile-Onset,Diabetes, Type 1,Insulin Dependent Diabetes Mellitus 1,Insulin-Dependent Diabetes Mellitus,Juvenile Onset Diabetes,Juvenile-Onset Diabetes Mellitus,Ketosis-Prone Diabetes Mellitus,Sudden-Onset Diabetes Mellitus
D005190 Family A social group consisting of parents or parent substitutes and children. Family Life Cycles,Family Members,Family Life Cycle,Family Research,Filiation,Kinship Networks,Relatives,Families,Family Member,Kinship Network,Life Cycle, Family,Life Cycles, Family,Network, Kinship,Networks, Kinship,Research, Family
D005260 Female Females
D006239 Haplotypes The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX. Haplotype
D006683 HLA-DQ Antigens A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases. HLA-DC Antigens,HLA-MB Antigens,HLA-DC,HLA-DQ,HLA-DS,HLA-DS Antigens,HLA-LB,HLA-LB Antigens,HLA-MB,Antigens, HLA-DC,Antigens, HLA-DQ,Antigens, HLA-DS,Antigens, HLA-LB,Antigens, HLA-MB,HLA DC Antigens,HLA DQ Antigens,HLA DS Antigens,HLA LB Antigens,HLA MB Antigens
D006684 HLA-DR Antigens A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS. HLA-DR,Antigens, HLA-DR,HLA DR Antigens
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D017508 Reunion One of the Indian Ocean Islands, east of Madagascar. Its capital is Saint-Denis. It was discovered in 1507 by the Portuguese and claimed by France in 1638. It was first colonized in 1662 as Isle de Bourbon but renamed Reunion in 1793. In 1946 it was made an overseas department of France. The name commemorates the reunion of the revolutionaries from Marseilles with the National Guard in Paris in 1792. (From Webster's New Geographical Dictionary, 1988, p1011; Room, Brewer's Dictionary of Names, 1992, p454; French Embassy)

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