Replication of association of the D-repeat polymorphism in asporin with osteoarthristis

It is not surprising that an association of a gene with a disease is found in some populations but not in others. Such diversity has been established for many common complex diseases with several explanations [5]. In this particular case, one explanation is the difference in the inclusion criteria used to recruit study participants. Whereas we recruited symptomatic OA patients with supporting radiographic evidence, Rodriguez-Lopez and colleagues used joint replacement surgery as inclusion criteria (Table 1).Another explanation is ethnic diversity, which is apparent in the very different allelic frequencies between the Spanish and Japanese populations. We question the authors' generalization of the three European populations (Spanish, Greek and UK) as 'European Caucasian', given the diverse frequencies of asporin alleles in the three populations [1,3,4] (Table 2), as well as their history and geography. The Spanish population in particular is distinct from the others; for example, the frequency of the common allele, Asp13 (D13), in the Spanish control groups shows statistically significant differences (p = 0.00088 versus UK; p = 0.021 versus Greek). The allelic frequency in hip OA also is very different.However, it is notable that in studies of knee OA for all three European populations, the allelic frequency of D13 is decreased and that of D14 is increased in the case group – the same trend observed in our Japanese study (Table 2). In all four populations, the odds ratios exceed 1. Given that the deviation of the odds ratio is random, the probability for its occurrence by chance is (1/2)4 = 1/16, which is substantially low. If we combine data for all three European populations, the association becomes significant (p = 0.030; odds ratio 1.26, 95% confidence interval 1.02 to 1.56). We believe that this estimation is valid because the inclusion criteria are the same, provided that the ethnicity is consistent as the Spanish group itself proposed. If so, the association