Association of the Frizzled-related protein gene with symptomatic osteoarthritis at multiple sites
Association of the Frizzled-related protein gene with symptomatic osteoarthritis at multiple sites
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DOI：
10.1002/art.20993
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发表时间：
2005-04-01
影响因子：
--
通讯作者：
Slagboom, PE
中科院分区：
文献类型：
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作者：
Min, JL;Meulenbelt, I;Slagboom, PE
Objective.目的：证实卷曲相关蛋白基因（FRZB）的2个变异体与髋关节骨关节炎（OA）的相关性，并研究这些变异体是否也与其他遗传性全身OA表型相关。2个变量的关联分析在随机抽取的1,369名受试者中进行了FRZB（R200 W和R324 G）试验（年龄55-70岁）（鹿特丹研究）对髋关节、手、脊柱、和膝关节，在白人先证者（年龄40-70岁）和他们的兄弟姐妹中，选择在多个部位存在原发性症状性OA。两种变体的等位基因频率在髋关节放射学OA（罗阿）受试者和对照组之间没有显著差异。与来自鹿特丹研究的对照组（0.08）相比，来自鹿特丹研究的全身性罗阿受试者（0.10）和来自遗传学、骨关节炎和进展研究的受试者（0.11）中R324 G变体G等位基因的频率显著增加。该G等位基因携带者对全身性罗阿（优势比[OR] 1.4，95%CI [95%CI] 0.9-1.9，P = 0.10）或家族性多部位症状性OA（优势比1.6，95%CI 1.1-2.3，P = 0.02）的易感性增加。我们的研究结果证实，FRZB基因的R324 G变体参与OA，并表明该变体在几种广义OA表型中的作用。一个更广泛的骨关节炎表型确实可以预期从遗传变异的骨骼发育的一个重要途径，如Wnt信号。
Objective. To confirm the association of 2 variants of the Frizzled- related protein gene (FRZB) with osteoarthritis (OA) of the hip, and to investigate whether these variants also associate with other heritable generalized OA phenotypes.Methods. An association analysis of 2 variants (R200W and R324G) of FRZB was performed in a random sample of 1,369 subjects (ages 55-70 years) from a population-based cohort (the Rotterdam Study) scored for radiographic characteristics of OA in the hip, hand, spine, and knee and in a patient population of Caucasian probands (ages 40-70 years) and their siblings selected for the presence of primary symptomatic OA at multiple sites.Results. The allele frequency of the 2 variants was not significantly different between subjects with hip radiographic OA (ROA) and controls. The frequency of the G allele of the R324G variant was significantly increased in subjects with generalized ROA from the Rotterdam Study (0.10) and in subjects from the Genetics, osteoARthritis and Progression study (0.11) compared with that in controls from the Rotterdam Study (0.08). Carriers of this G allele had increased susceptibility for generalized ROA (odds ratio [OR] 1.4, 95% confidence interval [95% CI] 0.9-1.9, P = 0.10) or familial symptomatic OA at multiple sites (OR 1.6, 95% CI 1.1-2.3, P = 0.02).Conclusion. Our results confirm that the R324G variant of the FRZB gene is involved in OA and indicate a role of this variant in several generalized OA phenotypes. A more extended OA phenotype may indeed be expected from genetic variation in an essential pathway of skeletal development such as Wnt signaling.