title: Meta-analysis of association between the ASPN D-repeat and osteoarthritis.
abstract: Osteoarthritis (OA) is the most common form of human arthritis. Genetic factors have been implicated in OA. It was reported that an aspartic acid (D)-repeat polymorphism in the gene encoding asporin (ASPN) was associated with OA of knee and hip joints in Japanese; in the three independent studies performed, the D14 allele of the ASPN polymorphism was over-represented and the D13 allele was under-represented. Subsequently, four replication studies, three in Europeans and one in Chinese populations, have been reported; however, they showed inconsistent results. To evaluate between-study heterogeneity and to estimate the common genetic effect of the D-repeat polymorphism on OA, we performed a meta-analysis of the five reports that include seven association studies, using the DerSimonian-Laird procedure. We detected association between knee OA and the susceptible D14 allele [P = 0.003, summary odds ratio (OR) = 1.46] with significant heterogeneity (P = 0.047) among the studies. We also detected positive association between knee OA and the protective D13 allele (P = 0.026, summary OR = 0.84) with significant heterogeneity (P = 0.040) among the studies. Because of significant heterogeneity, we stratified the studies by ethnicity. We detected positive association between knee OA and the D14 allele (P = 0.0000013, summary OR = 1.95) with non-significant heterogeneity (P = 0.535) in Asian populations. In hip OA, significant heterogeneity was identified and there was no positive association for any allele in any comparison. The present results suggest that the association of the ASPN D14 allele and knee OA has global relevance, but that its effect has ethnic differences.
authors.affiliation: Laboratory for Statistical Analysis, SNP Research Center, RIKEN, Tokyo 108-8639, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Dongquan
authors.initials: D
authors.lastname: Shi
authors.forename: Maria
authors.initials: M
authors.lastname: Tzetis
authors.forename: Julio
authors.initials: J
authors.lastname: Rodriguez-Lopez
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Aspasia
authors.initials: A
authors.lastname: Tsezou
authors.forename: Antonio
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: John
authors.initials: J
authors.lastname: Loughlin
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000483:Alleles; D001241:Aspirin / Q000494:pharmacology; D015992:Body Mass Index; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006615:Hip / Q000473:pathology; D006801:Humans; D007717:Knee / Q000473:pathology; D008297:Male; D015233:Models, Statistical; D016017:Odds Ratio; D010003:Osteoarthritis / Q000378:metabolism*; D011110:Polymorphism, Genetic; D012984:Software
chemical_list: C439889:ASPN protein, human; D016326:Extracellular Matrix Proteins; D001241:Aspirin