AI Article Synopsis
- The study aimed to find genetic factors linked to primary hip and knee osteoarthritis (OA) in Finnish families with multiple affected members.
- Genome-wide analysis on 15 families led to the identification of a susceptibility locus on chromosome 2q21, alongside a specific insertion variant (rs11446594) that enhances the binding efficiency of certain transcription factors.
- This novel variant may play a crucial role in maintaining healthy cartilage, highlighting its potential significance in understanding and addressing OA.
Article Abstract
Objective: The aim of the study was to identify genetic variants predisposing to primary hip and knee osteoarthritis (OA) in a sample of Finnish families.
Methods: Genome wide analysis was performed using 15 independent families (279 individuals) originating from Central Finland identified as having multiple individuals with primary hip and/or knee OA. Targeted re-sequencing was performed for three samples from one 33-member, four-generation family contributing most significantly to the LOD score. In addition, exome sequencing was performed in three family members from the same family.
Results: Genome wide linkage analysis identified a susceptibility locus on chromosome 2q21 with a multipoint LOD score of 3.91. Targeted re-sequencing and subsequent linkage analysis revealed a susceptibility insertion variant rs11446594. It locates in a predicted strong enhancer element region with maximum LOD score 3.42 under dominant model of inheritance. Insertion creates a recognition sequence for ELF3 and HMGA1 transcription factors. Their DNA-binding affinity is highly increased in the presence of A-allele compared to wild type null allele.
Conclusion: A potentially novel functional OA susceptibility variant was identified by targeted re-sequencing. This variant locates in a predicted regulatory site and creates a recognition sequence for ELF3 and HMGA1 transcription factors that are predicted to play a significant role in articular cartilage homeostasis.
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| http://dx.doi.org/10.1016/j.joca.2015.10.019 | DOI Listing |
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