title: Association of CYP17 with HLA-B27-negative seronegative spondyloarthropathy in Japanese males.
abstract: Susceptibility genes for seronegative spondyloarthropathy (SNSA) other than HLA-B27 remain unclarified. Sex hormones are implicated in the pathogenesis of SNSA. Cytochrome P450c17a (CYP17) is a key regulator of androgen biosynthesis, and a single nucleotide polymorphism (SNP) in the 5'-untranslated region of the CYP17 gene (CYP17), -34C > T, is associated with variety of diseases. We have investigated the association between the CYP17 SNP and SNSA in Japanese males. Genomic DNA was extracted from 149 Japanese male SNSA patients and 380 controls. The CYP17 SNP was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Allelic and genotypic frequencies of the SNP were compared between SNSA patients and controls, and within SNSA patients. We also computed haplotype frequencies using an expectation-maximization algorithm, analyzed the difference between SNSA and control groups, and examined the potential association of other known SNPs in the CYP17 gene. The frequency of the -34T allele was significantly increased in HLA-B27-negative SNSA, but not in total or HLA-B27-positive SNSA when compared to controls. The T allele was more prevalent in HLA-B27-negative SNSA than in HLA-B27-positive SNSA, and the T/T genotype was over-represented in HLA-B27-negative SNSA. Haplotype analysis did not demonstrate more significant association. The CYP17 SNP is associated with SNSA in HLA-B27-negative Japanese males.
authors.affiliation: Department of Orthopaedic Surgery, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Mori
authors.forename: Hideki
authors.initials: H
authors.lastname: Kizawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Ushiyama
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Chano
authors.forename: Hisashi
authors.initials: H
authors.lastname: Inoue
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Okabe
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Matsusue
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005787:Gene Frequency; D005838:Genotype; D015796:HLA-B27 Antigen / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D025242:Spondylarthropathies / Q000097:blood / Q000235:genetics* / Q000473:pathology; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
chemical_list: D015796:HLA-B27 Antigen; D004247:DNA; D013254:Steroid 17-alpha-Hydroxylase