Association of the MSX2 gene polymorphisms with ankylosing spondylitis in Japanese.
Several genes have been implicated in the etiology of ankylosing spondylitis (AS); however, the significance of these genes except HLA-B27 remains to be elucidated. In this study, we examined the association of AS with novel candidate genes and previously reported genes other than HLA-B27. We examined a total of 45 single nucleotide polymorphisms (SNPs) in 15 genes by a sequential screening. We first genotyped 170 Japanese AS patients and 896 controls for the SNPs (first screen). Then, we genotyped eight SNPs with P < 0.05 in the first screen for 108 additional Japanese patients (second screen). We checked the replication of the association of the most significant SNP by genotyping 219 Taiwanese AS patients and 185 controls. When the first and second screens were combined, four SNPs showed nominal significance of P < 0.05. An intronic SNP (IVS1 + 996G > A) in MSX2, a novel candidate gene, showed the most significant association (P = 0.0030). The association was not replicated in our Taiwanese population; however, there was the same trend with the Japanese population in the allelic frequency distribution of the SNP. In the genes previously reported to have association with AS, only one synonymous SNP, c.963T > G in ANKH, showed a marginal association in the Japanese population (P = 0.045).
Furuichi
Tatsuya
T
Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
Maeda
Koichi
K
Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.|Department of Orthopaedics Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Chou
Chung-Tei
CT
Division of Allergy-Immunology-Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Liu
Yu-Fen
YF
Genome Research Center, National Yang-Ming University, Taipei, Taiwan.
Liu
Ting-Chun
TC
Genome Research Center, National Yang-Ming University, Taipei, Taiwan.
Miyamoto
Yoshinari
Y
Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
Takahashi
Atsushi
A
Laboratory for Statistical Analysis, SNP Research Center, RIKEN, Tokyo, Japan.
Mori
Kanji
K
Department of Orthopaedic Surgery, Shiga University of Medical Science, Otsu, Japan.
Ikari
Katsunori
K
Institute of Rheumatology, Tokyo Woman's Medical University, Tokyo, Japan.
Kamatani
Naoyuki
N
Laboratory for Statistical Analysis, SNP Research Center, RIKEN, Tokyo, Japan.|Institute of Rheumatology, Tokyo Woman's Medical University, Tokyo, Japan.
Kurosawa
Hisashi
H
Department of Orthopaedics Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Inoue
Hisashi
H
Department of Orthopaedics Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Tsai
Shih-Feng
SF
Genome Research Center, National Yang-Ming University, Taipei, Taiwan.|Division of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
Ikegawa
Shiro
S
Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. sikegawa@ims.u-tokyo.ac.jp.
D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D007564:Japan; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D028061:Phosphate Transport Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000473:pathology
C498770:ANKH protein, human; D018398:Homeodomain Proteins; C084119:MSX2 protein; D028061:Phosphate Transport Proteins