Variants within the MMP3 gene and patellar tendon properties in vivo in an asymptomatic population

Background/aim Gene variants encoding for proteins involved in homeostatic processes within tendons may influence its material and mechanical properties in humans. The purpose of this study was to examine the association between three polymorphisms of the MMP3 gene, (rs679620, rs591058 and rs650108) and patellar tendon dimensional and mechanical properties in vivo. Methods One hundred and sixty, healthy, recreationally-active, Caucasian men and women, aged 18–39 were recruited. MMP3 genotype determined using real-time PCR was used to select 84 participants showing greatest genetic differences to complete phenotype measurements. Patellar tendon dimensions (volume) and functional (elastic modulus) properties were assessed in vivo using geometric modelling, isokinetic dynamometry, electromyography and ultrasonography. Results No significant associations were evident between the completely linked MMP3 rs591058 and rs679620 gene variants, and closely linked rs650108 gene variant, and either patellar tendon volume (rs679620, P = 0.845; rs650108, P = 0.984) or elastic modulus (rs679620, P = 0.226; rs650108, P = 0.088). Similarly, there were no associations with the Z-score that combined those dimension and functional properties into a composite value (rs679620, P = 0.654; rs650108, P = 0.390). Similarly, no association was evident when comparing individuals with/without the rarer alleles (P > 0.01 in all cases). Conclusions Patellar tendon properties do not seem to be influenced by the MMP3 gene variants measured. Although these MMP3 gene variants have previously been associated with the risk of tendon pathology, that association is unlikely to be mediated via underlying tendon dimensional and functional properties

Analysis of the binding site architecture of monoclonal antibodies to morphine by using competitive ligand binding and molecular modeling.

Abstract The structural features of mAb directed against the opiate morphine were analyzed by using competitive ligand analog-binding studies, examination of the V region amino acid sequence, and computer-aided molecular modeling of the fragment V region. The antibody response in BALB/c mice to morphine is relatively restricted, in that all of the mAb examined in this study contained the same lambda L chain and very similar H chain V regions. A three-dimensional model of the antimorphine-binding site was constructed by using computational and graphic display techniques. Each of the six complementary-determining regions was constructed by using fragment replacement methods employing canonical loop conformations of known "parent" structures. Experimental competitive ligand-binding data and theoretical modeling suggest that a charged glutamate residue at position H:50 and aromatic side chains of residues H:33W, H:47W, H:58F, H:95W, H:101iY, and L:91W are key features in ionic and hydrophobic interactions with the ligand. This study represents the first use of theoretical and experimental modeling techniques to describe the Ag-binding site of a mouse fragment V region containing a lambda L chain.</jats:p