Association of COA1 with Patellar Tendonitis: A Genome-wide Association Analysis

Abstract

PurposeIt is unknown why some athletes develop patellar tendinopathy and others do not, even when accounting for similar workloads between individuals. Genetic differences between these two populations may be a contributing factor. The purpose of this work was to screen the entire genome for genetic markers associated with patellar tendinopathy.MethodsGenome-wide association (GWA) analyses were performed utilizing data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. Patellar tendinopathy cases were identified based on electronic health records from KPRB and UK Biobank. GWA analyses from both cohorts were tested for patellar tendinopathy using a logistic regression model adjusting for sex, height, weight, age, and race/ethnicity using allele counts for single nucleotide polymorphisms. The data from the two GWA studies (KPRB and UK Biobank) were combined in a meta-analysis.ResultsThere were a total of 1670 cases of patellar tendinopathy and 293,866 controls within the two cohorts. Two single nucleotide polymorphisms located in the intron of the cytochrome c oxidase assembly factor 1 (COA1) gene showed a genome-wide significant association in the meta-analysis.ConclusionsGenetic markers in COA1 seem to be associated with patellar tendinopathy and are potential risk factors for patellar tendinopathy that deserve further validation regarding molecular mechanisms.

The Best Current Research on Patellar Tendinopathy: A Review of Published Meta-Analyses

“…A systematic search of PubMed for meta-analyses on patellar tendinopathy was performed, leading to the identification of a total of 21 studies that met the inclusion criteria [ 14 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ] ( Table 1 ). Regarding the origin of the meta-analyses, three were from the United States, two were from Italy, one was from New Zealand, three were from the United Kingdom, three were from Australia, one was from China, one was from Ireland, one was from Canada, one was from the Netherlands, one was from Brazil, one was from Spain, one was from Finland, and one was from Belgium.…”

“…Recent investigations have identified potential genetic markers in the COA1 gene that may be associated with patellar tendinopathy, suggesting a potential genetic predisposition to this condition. Despite these preliminary findings, evidence on the genetic underpinnings of tendinopathies remains limited, and the field requires further exploration to identify reproducible genetic markers linked to these conditions [ 31 ].…”

Are commercial genetic injury tests premature?

“…Some studies, however, did use more stringent inclusion criteria, for example the inclusion of only MRI confirmed full-thickness supraspinatus or infraspinatus rotator cuff tears as cases. 85 Only one polymorphism each was identified to modulate the risk of De Quervain's tenosynovitis (rs35360670, C > A) and shoulder dislocation/instability (rs12913965, C > T), 75,81 two each with Patellar Tendinopathy (rs149047058, G > A; rs142128304, G > A), ankle injury (chr21:47156779:D; rs13286037, T > A), MCL (rs80351309, C > T; rs6083471, T > C) and Plantar Fascial Disorders (chr5:118704153:D; rs62051384, C > T), 74,77,78,80 and three polymorphisms with ACL and PCL injuries (rs144051132, T > A; rs186727643, C > T; rs188099931, A > G) 73 (Table 2 and Table S6). When only cases with clinically confirmed, by reviewing imaging and/or surgical records, partial or complete ACL ruptures were included, none of the three polymorphisms that associated with ACL and PCL injuries using only the ICD and CPT codes were identified.…”

“…The specific set of polymorphisms used in each test has not been listed on its webpage; however, the full text of 13 peer-reviewed published articles for many of the identified polymorphisms is provided (Table 2, Tables S6 and S7; accessed during July 2022). 47,[73][74][75][76][77][78][79][80][81][82][83][84] Concussion, which is not a musculoskeletal tissue injury, as well as stress fracture risk and bone mineral density, which are determined by an algorithm, were excluded from this review. We identified and included an additional four GWAS rotator cuff injury publications in the review (Table 2 and Table S7).…”

“…These include rotator cuff injury, runner's knee, Achilles tendon injury, ACL and PCL injury, concussion, ankle injury, plantar fasciitis, iliotibial band syndrome, patellar tendinopathy, de Quervain's Tenosynovitis, MCL injury, shoulder instability, stress fracture risk, and bone mineral density (Table 2) (http://www.axgen.us/what-you-get, accessed during July 2022). The specific set of polymorphisms used in each test has not been listed on its webpage; however, the full text of 13 peer‐reviewed published articles for many of the identified polymorphisms is provided (Table 2, Tables S6 and S7; accessed during July 2022) 47,73–84 . Concussion, which is not a musculoskeletal tissue injury, as well as stress fracture risk and bone mineral density, which are determined by an algorithm, were excluded from this review.…”