Carroll G J, Breidahl W H, Jazayeri J
ArthroCare Pty Ltd, Mount Lawley, Western Australia, Australia.
Osteoarthritis Cartilage. 2009 Jul;17(7):891-5. doi: 10.1016/j.joca.2009.01.003. Epub 2009 Jan 21.
Previous studies of patients with primary hand and ankle osteoarthritis (OA) have suggested the presence of two major polyarticular OA (POA) phenotypes, designated Type 1 and Type 2. The former, characterised by sentinel distal interphalangeal (IP) (DIP) or proximal IP (PIP) joint OA resembles generalised OA (GOA), whereas the latter characterised by sentinel metacarpophalangeal (MCP)2,3 OA, resembles the arthropathy associated with hereditary haemochromatosis (HH). The aim of this study was to validate these putative phenotypes and to further investigate their clinical and genetic characteristics.
Newly referred patients had X-rays if pre-determined clinical criteria for OA in hand and other joints were met. Subjects were assigned to the putative Type 1 POA (T1POA) or Type 2 POA (T2POA) phenotypes if radiological criteria were satisfied. Human haemochromatosis (HFE) gene mutations were determined in buffy-coat DNA by polymerase chain reaction amplification, followed by restriction enzyme cleavage and analysis on a 3% agarose gel. The significance of differences was determined by Chi-square test or by Fisher's exact test.
Sixty-seven patients fulfilled criteria for inclusion in this study; 39 (6M, 33F) for T1POA and 28 (18M, 10F) for T2POA. A statistically significant difference in gender was observed (64% male in the T2POA subset, P<0.0001). Heberden's nodes (HNs) were found in 34 of the 39 Type 1 subjects, but in only nine of the 28 Type 2 subjects (P<0.0001). HFE gene mutations were found in nine of the 39 Type 1 subjects (23%), whereas 21 of the 28 Type 2 subjects had a single HFE gene mutation (75%, P<0.0001).
These findings confirm the hitherto hypothetical proposition of a T1POA phenotype conforming to nodal GOA (NGOA) and a T2POA phenotype closely resembling the arthropathy described in haemochromatosis (HH).
先前对原发性手部和踝关节骨关节炎（OA）患者的研究表明存在两种主要的多关节型OA（POA）表型，分别命名为1型和2型。前者以标志性的远端指间关节（DIP）或近端指间关节（PIP）OA为特征，类似于全身性OA（GOA），而后者以标志性的掌指关节（MCP）2,3 OA为特征，类似于与遗传性血色素沉着症（HH）相关的关节病。本研究的目的是验证这些假定的表型，并进一步研究它们的临床和遗传特征。
如果新转诊患者符合手部和其他关节OA的预定临床标准，则进行X线检查。如果满足放射学标准，则将受试者分配到假定的1型POA（T1POA）或2型POA（T2POA）表型。通过聚合酶链反应扩增测定血沉棕黄层DNA中的人类血色素沉着症（HFE）基因突变，然后进行限制性内切酶切割并在3%琼脂糖凝胶上进行分析。差异的显著性通过卡方检验或费舍尔精确检验确定。
67例患者符合本研究的纳入标准；39例（6例男性，33例女性）为T1POA，28例（18例男性，10例女性）为T2POA。观察到性别存在统计学显著差异（T2POA亚组中男性占64%，P<0.0001）。在39例1型受试者中有34例发现赫伯登结节（HNs），但在28例2型受试者中仅9例发现（P<0.0001）。在39例1型受试者中有9例发现HFE基因突变（23%），而28例2型受试者中有21例有单个HFE基因突变（75%，P<0.0001）。
这些发现证实了迄今为止关于符合结节性GOA（NGOA）的T1POA表型和与血色素沉着症（HH）中描述的关节病非常相似的T2POA表型的假设命题。
