HLA DQA1 genotypes and its interaction with HLA DQB1 in Chinese IDDM living in Taiwan.
To study the role of the HLA DQA1 gene and its interaction with DQB1 in the susceptibility of IDDM, subjects with insulin-dependent (type 1) diabetes mellitus and non-diabetic unrelated controls were recruited from a Chinese population living in northern Taiwan. HLA DQA1 exon 2 was enzymatically amplified by polymerase chain reaction. HLA DQA1 alleles were diagnosed by dot blotting and hybridization with 11 sequence-specific oligonucleotide probes. Among all the DQA1 alleles, DQA1*0301 and DQA1*0501 were more frequent while DQA1*0102, DQA1*0103 and DQA1*0601 were less frequent in Chinese with IDDM than in controls. Among the DQA1 genotypes, only DQA1*0301/0301 and DQA1*0301/0501 were associated with increased risk to IDDM while DQA1*0301/0601 and DQA1*0102/0103 were protective against IDDM in our population. As the cell surface HLA DQ molecules were formed from each DQA1 and DQB1 alleles either in cis- or trans-position, the numbers of susceptible HLA DQ alpha beta heterodimers were then derived from the genotypes of HLA DQA1/DQB1 in each person. The numbers of the possible diabetogenic DQ alpha beta dimers correlated with the degree of risk to IDDM (r = 0.92) but were not statistically significant (p > 0.05). Subjects with absence of diabetogenic HLA DQ molecules were resistant to developing IDDM while subjects with two or more forms of diabetogenic DQ molecules were associated with increased risk to IDDM. In conclusion, both DQA1 and DQB1 genes, which determine the formation of susceptible DQ alpha beta heterodimers, were significantly associated with IDDM in Chinese subjects living in Taiwan.
Chuang
L M
LM
Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Republic of China.
Jou
T S
TS
Wu
H P
HP
Chang
H M
HM
Tsai
W Y
WY
Hsieh
R P
RP
Chen
K H
KH
Lin
B J
BJ
Tai
T Y
TY
D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005091:Exons; D005787:Gene Frequency; D005838:Genotype; D006683:HLA-DQ Antigens / Q000737:chemistry / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006801:Humans; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D013624:Taiwan
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes