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1.  Two Single-Nucleotide Polymorphisms in ADAM12 Gene Are Associated with Early and Late Radiographic Knee Osteoarthritis in Estonian Population 
Arthritis  2013;2013:878126.
Objectives. To investigate associations of selected single-nucleotide polymorphisms (SNPs) in ADAM12 gene with radiographic knee osteoarthritis (rKOA) in Estonian population. Methods. The rs3740199, rs1871054, rs1278279, and rs1044122 SNPs in ADAM12 gene were genotyped in 438 subjects (303 women) from population-based cohort, aged 32 to 57 (mean 45.4). The rKOA features were evaluated in the tibiofemoral joint (TFJ) and patellofemoral joint. Results. The early rKOA was found in 51.4% of investigated subjects (72% women) and 12.3% of participants (63% women) had advanced stage of diseases. The A allele of synonymous SNP rs1044122 was associated with early rKOA in TFJ, predominantly with the presence of osteophytes in females (OR 1.57; 95% CI 1.08–2.29, P = 0.018). The C allele of intron polymorphism rs1871054 carried risk for advanced rKOA, mostly to osteophyte formation in TFJ in males (OR 3.03; 95% CI 1.11–7.53, P = 0.018). Also the CCAA haplotype of ADAM12 was associated with osteophytosis, again mostly in TFJ in males (P = 0.014). For rs3740199 and rs1278279, no statistically significant associations were observed. Conclusion.  ADAM12 gene variants are related to rKOA risk during the early and late stages of diseases. The genetic risk seems to be predominantly associated with the appearance of osteophytes—a marker of bone remodelling and neochondrogenesis.
doi:10.1155/2013/878126
PMCID: PMC3625563  PMID: 23606964
3.  Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium 
Objective
To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes.
Methods
Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. To investigate whether different OA definitions result in different association results, we created hip OA definitions used within the consortium in the Rotterdam Study-I and tested the association of hip OA with gender, age and BMI using one-way ANOVA. For radiographic OA, we standardized the hip, knee and hand ROA definitions and calculated prevalence's of ROA before and after standardization in 9 cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment.
Results
In this consortium, all studies with symptomatic OA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee, hip and hand radiographic OA 5, 4 and 7 different definitions were used, respectively. Different hip OA definitions do lead to different association results. For example, we showed in the Rotterdam Study-I that hip OA defined as “at least definite JSN and one definite osteophyte” was not associated with gender (p=0.22), but defined as “at least one definite osteophyte” was significantly associated with gender (p=3×10−9). Therefore, a standardization process was undertaken for radiographic OA definitions. Before standardization a wide range of ROA prevalence's was observed in the 9 cohorts studied. After standardization the range in prevalence of knee and hip ROA was small. Standardization of SOA phenotypes was not possible due to the case-control design of the studies.
Conclusion
Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies.
doi:10.1016/j.joca.2010.10.027
PMCID: PMC3236091  PMID: 21059398
4.  Large Scale Replication Study of the Association between HLA Class II/BTNL2 Variants and Osteoarthritis of the Knee in European-Descent Populations 
PLoS ONE  2011;6(8):e23371.
Osteoarthritis (OA) is the most common form of arthritis and a major cause of disability. This study evaluates the association in Caucasian populations of two single nucleotide polymorphisms (SNPs) mapping to the Human Leukocyte Antigen (HLA) region and deriving from a genome wide association scan (GWAS) of knee OA in Japanese populations. The frequencies for rs10947262 were compared in 36,408 controls and 5,749 knee OA cases from European-descent populations. rs7775228 was tested in 32,823 controls and 1,837 knee OA cases of European descent. The risk (major) allele at rs10947262 in Caucasian samples was not significantly associated with an odds ratio (OR)  = 1.07 (95%CI 0.94 -1.21; p = 0.28). For rs7775228 the meta-analysis resulted in OR = 0.94 (95%CI 0.81-1.09; p = 0.42) for the allele associated with risk in the Japanese GWAS. In Japanese individuals these two SNPs are in strong linkage disequilibrium (LD) (r2 = 0.86) with the HLA class II haplotype DRB1*1502 DQA1*0103 DQB1*0601 (frequency 8%). In Caucasian and Chinese samples, using imputed data, these SNPs appear not to be in LD with that haplotype (r2<0.07). The rs10947262 and rs7775228 variants are not associated with risk of knee OA in European descent populations and they do not appear tag the same HLA class II haplotype as they do in Japanese individuals.
doi:10.1371/journal.pone.0023371
PMCID: PMC3154440  PMID: 21853121

Results 1-4 (4)