title: Association of the formiminotransferase N-terminal sub-domain containing gene and thrombospondin, type 1, domain-containing 7A gene with the prevalence of vertebral fracture in 2427 consecutive autopsy cases.
abstract: We previously reported 2 osteoporosis-susceptibility genes--formiminotransferase N-terminal sub-domain containing gene (FONG) and thrombospondin, type 1, domain-containing 7A (THSD7A)--in which we identified two common single-nucleotide polymorphisms, rs7605378 (FONG) and rs12673692 (THSD7A). The former was associated with a predisposition to osteoporosis and the latter with bone mineral density. To further elucidate the importance of these polymorphisms in the pathogenesis of osteoporosis, we examined their association with the incidence of vertebral fracture. DNA extracted from the renal cortex of 2427 consecutive Japanese autopsies (1331 men, mean age: 79 years; 1096 women, mean age: 82 years) were examined in this study. The presence or absence of vertebral fracture during each subject's lifetime was determined by a thorough examination of the clinical records, as well as autopsy reports. After adjustments for sex and age at autopsy, logistic regression analysis revealed that homozygotes for the risk alleles of rs7605378 (A-allele) or rs12673629 (A-allele) possess an increased risk of vertebral fracture. The subjects simultaneously homozygous for both the risk alleles of rs7605378 (AA genotype) and rs12673629 (AA genotype) showed significantly higher risk of vertebral fracture (odds ratio 2.401, 95% confidence interval 1.305-4.416, P = 0.0048) than those who had at least one non-risk allele of either rs7605378 (AC/CC genotypes) or rs12673629 (AG/GG genotypes). The results suggest that Japanese subjects homozygous for the risk alleles of rs7605378 and rs12673629 have a higher risk of vertebral fracture.
authors.affiliation: Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
authors.forename: Heying
authors.initials: H
authors.lastname: Zhou
authors.forename: Seijiro
authors.initials: S
authors.lastname: Mori
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Kou
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Fuku
authors.forename: Makiko
authors.initials: M
authors.lastname: Naka Mieno
authors.forename: Naoko
authors.initials: N
authors.lastname: Honma
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.forename: Motoji
authors.initials: M
authors.lastname: Sawabe
authors.forename: Masashi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Ito
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D005260:Female; D005838:Genotype; D051042:Glutamate Formimidoyltransferase / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D019877:Hydroxymethyl and Formyl Transferases / Q000235:genetics*; D008297:Male; D016103:Spinal Fractures / Q000235:genetics*; D019699:Thrombospondins / Q000235:genetics*
chemical_list: C546399:THSD7A protein, human; D019699:Thrombospondins; C560598:FTCDNL1 protein, human; D019877:Hydroxymethyl and Formyl Transferases; D051042:Glutamate Formimidoyltransferase