Single-nucleotide polymorphisms in the class II region of the major histocompatibility complex in Japanese patients with immunoglobulin A nephropathy.
Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis of unknown etiology and pathogenesis. Immunogenetic studies have not conclusively indicated that human leukocyte antigen (HLA) is involved. As a first step in investigating a possible relationship between HLA class II genes and IgAN, we analyzed the extent of linkage disequilibrium (LD) in this region of chromosome 6p21.3 in a Japanese test population and found extended LD blocks within the class II locus. We designed a case-control association study of single-nucleotide polymorphisms (SNPs) in each of those LD blocks, and determined that SNPs located in the HLA- DRA gene were significantly associated with an increased risk of IgAN ( P = 0.000001, odds ratio = 1.91 [95% confidence interval 1.46-2.49]); SNPs in other LD blocks were not. Our data imply that some haplotype of the HLA- DRA locus has an important role in the development of IgAN in Japanese patients.
Akiyama
Fumihiro
F
Human Genome Center, The Institute of Medical Science, University of Tokyo, Japan.
Tanaka
Toshihiro
T
Yamada
Ryo
R
Ohnishi
Yozo
Y
Tsunoda
Tatsuhiko
T
Maeda
Shiro
S
Takei
Takashi
T
Obara
Wataru
W
Ito
Kyoko
K
Honda
Kazuho
K
Uchida
Keiko
K
Tsuchiya
Ken
K
Nitta
Kosaku
K
Yumura
Wako
W
Nihei
Hiroshi
H
Ujiie
Takashi
T
Nagane
Yutaka
Y
Miyano
Satoru
S
Suzuki
Yasushi
Y
Fujioka
Tomoaki
T
Narita
Ichiei
I
Gejyo
Fumitake
F
Nakamura
Yusuke
Y
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059805:HLA-DR alpha-Chains; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains