ASSOCIATION ANALYSIS OF MATRILIN-1 GENE GENOTYPES AND OSTEOARTHRITIS

Background: It has been suggested that genotypic variation in the gene (1p35) which encodes the matrilin-1 (MATN-1) protein may be involved in the development of hip osteoarthritis (OA).Objectives: To determine if there is any association between the MATN-1 genotypes and different types of OA.Methods: One hundred and nineteen controls and 178 unrelated OA patients (Erosive and non-erosive hand OA, knee, hip, cervical, lumbar and generalized OA) of 3 ethnic groups were studied. The MATN-1 microsatellite in the 3'' untranslated region was amplified by PCR. The size of the amplification products was determined by capilar electrophoresis in a DNA Genetic Analizer. Association analysis between genotype distribution and groups was done by Pearson c2 test and by likelihood ratio association test. A logistic regression model was used to adjust for covariables. The strength of association between a genotype and the presence of OA was estimated by odds ratio (OR) with 95% confidence intervals (95% CI). P values ≤0,05 were considered significant. Statistical analysis were performed by Info-Gen 1.0. softwareResults: We identified 4 alleles according to their basepair (bp) length: A1= 110 bp; A2= 108 bp; A3=106 bp and A6=104 pb. The observed heterozygosity (n=297) was 0,49. Genotypic frequencies –overall and when discriminating by cases and controls- were not significantly different from that expected for a population in Hardy-Weinberg equilibrium (p=0,50; p=0,64 and p=0,61 respectively). Overall, the most frequent genotype was A1/A2 (43.1%). No significant difference in genotype distribution was found between OA and controls in the global analysis and when controlling by ethnic group, sex and age categories. When incorporating grade of occupation to the regression model analysis, patients with erosive OA and genotype A2/A2 presented an OR of 25,8 (95% CI 3,26-203,9; p=0,0007) when comparing against genotype A1/A1. The corresponding OR for patients with genotype A2/A2 and OA in first carpometacarpal joint and in distal and/or proximal interphalangeal joints was 9,73 (95% CI 1,72- 54,9; p=0,005) and 9,2 respectively (95% CI 1,42-59,5; p=0,0009). We found no association among genotypes and hip, cervical, knee, lumbar or generalized OA.Conclusion: There is no difference in the frequency of the genotypes in any ethnic group, therefore population stratification may not be influencing locus 1p35 in this sample. We find association between genotype A2/A2 and the presence of erosive hand OA, first carpometacarpal OA and distal and/or proximal interphalangeal joints. The occupation, related to the intensity of hand work, should be taken into account as an influencing factor in these patients.References: 1. Strusberg I, Tabares S, Sembaj A, del Castillo I, Villamar M, Strusberg AM, Moreno Barral J. "Association analysis of genotypic frequencies of matrilin-1 gene in patients with osteoarthritis. Clinical and Experimental Rheumatology 2002;20:543-5. ISSN 0392-856X.Citation: Ann Rheum Dis, volume 64, supplement III, year 2005, page 118Session: Genomics, genetics basis of disease and HLA/T cell recognition