Biomarkers associated with clinical phenotypes of hand osteoarthritis in a large multigenerational family: the CARRIAGE family study.
OBJECTIVE
To evaluate biological markers as potential quantitative traits of clinical osteoarthritis (OA) in a large multigenerational family in the Carolinas of the USA known as the CARRIAGE (CARolinas Region Interaction of Aging, Genes and Environment) family.


METHODS
During a series of three family reunions over 6 years, we ascertained 365 family members. We performed clinical hand examinations (n=287), and obtained sera (n=278) for seven OA-related biomarkers [type IIA collagen N-propeptide (PIIANP), type II procollagen carboxy-propeptide (CPII), neoepitope from cleavage of CII (C(2)C), cartilage oligomeric matrix protein (COMP), hyaluronan (HA), high-sensitive C-reactive protein (hs-CRP), and glycated serum protein (GSP)]. Three hand OA definitions were evaluated--clinical ACR (American College of Rheumatology) and GOGO (Genetics of Generalized OA) criteria, and any single hand joint involvement. Non-hand OA was defined as a negative hand examination for OA but varying prevalence of joint symptoms; the control group was defined as having neither symptoms nor evidence for clinical hand OA.


RESULTS
Mean lnHA, lnCOMP, and lnhs-CRP were significantly higher in the hand OA group, compared with the non-hand OA or control group. Adjusted for age and sex, mean lnPIIANP (a collagen II synthesis marker) was significantly lower in the hand OA group compared with the other groups. Among those without clinical hand OA, GSP was associated with hand joint symptoms.


CONCLUSIONS
This is the first report, to our knowledge, showing an association of OA biomarkers and hand OA based on physical examination alone. Analyses using these biomarkers as quantitative traits could reveal novel genetic loci and facilitate exploration of the genetic susceptibility to OA.
Chen
H-C
HC
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Shah
S
S
Stabler
T V
TV
Li
Y-J
YJ
Kraus
V B
VB
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D064236:Cartilage Oligomeric Matrix Protein; D024043:Collagen Type II / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005190:Family / Q000208:ethnology; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006225:Hand / Q000000981:diagnostic imaging; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D064235:Matrilin Proteins; D008875:Middle Aged; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D011446:Prospective Studies; D011859:Radiography; D012307:Risk Factors; D014481:United States
D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D006820:Hyaluronic Acid; D002097:C-Reactive Protein