MICA gene polymorphism in HBDI multiplex families.
T1DM is a disease that affects pancreatic beta cells and results in severe insulin depletion. T1DM is a multigenic disease, and the strongest genetic association with this disease is shown by the genes in MHC class II, namely, DQA1 and DQB1. The other gene that has been implicated in susceptibility to T1DM is the MICA gene that lies within the MHC class I region. This gene has been investigated in many autoimmune diseases, including T1DM, in case-control as well as in family studies. The aim of our study was to test the transmission of MICA microsatellite alleles from unaffected parents to T1DM- affected offspring in HBDI multiplex nuclear families. We also looked at the transmission of MICA alleles together with high-risk DQA1-DQB1 haplotypes to determine the independent transmission of MICA alleles. We observed that MICA6 and MICA9 are transmitted to affected offspring less frequently than expected, and MICA5.1 was more frequently transmitted. DQA1 and DQB1 high-risk haplotypes were transmitted more frequently than expected and DQ6, which is a protective haplotype, was less frequently transmitted to affected offspring. Analysis of MICA-DQA1-DQB1 transmission showed that certain MICA alleles are preferably transmitted as a part of high-risk haplotypes, which might indicate that MICA together with high-risk HLA is associated with T1DM in this family material. However, this latter analysis should be repeated on a larger family sample.
Nikitina-Zake
Liene
L
Immunogenetics, Department of Molecular Medicine, CMM L8:00, Karolinska Sjukhuset, K1, 17176, Stockholm, Sweden.
Ghaderi
Mehran
M
Park
Yongsoo
Y
Babu
Sunanda
S
Eisenbarth
George
G
Sanjeevi
Carani B
CB
D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009679:Nuclear Family; D010375:Pedigree; D011110:Polymorphism, Genetic; D014481:United States; D044465:White People
D005819:Genetic Markers; D006683:HLA-DQ Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A