A genome-wide association study for shoulder impingement and rotator cuff disease.

BACKGROUND: The purpose of the study was to identify genetic variants associated with rotator cuff disease by performing a genome-wide association study (GWAS) for shoulder impingement using the UK Biobank (UKB) cohort and then combining the GWAS data with a prior GWAS for rotator cuff tears. The loci identified by the GWAS and meta-analysis were examined for changes in expression following rotator cuff tearing using RNA sequencing. METHODS: A GWAS was performed using data from UKB with 3864 cases of shoulder impingement. The summary statistics from shoulder impingement and a prior study on rotator cuff tears were combined in a meta-analysis. Also, the previous association of 2 single-nucleotide polymorphisms (SNPs) with shoulder impingement from a published GWAS using the UKB was tested. Rotator cuff tendon biopsies were obtained from 24 patients with full-thickness rotator cuff tears who underwent arthroscopic rotator cuff repair (cases) and 9 patients who underwent open reduction internal fixation for a proximal humeral fracture (controls). Total RNA was extracted and differential gene expression was measured by RNA sequencing for genes with variants associated with rotator cuff tearing. RESULTS: The shoulder impingement GWAS identified 4 new loci: LOC100506457, LSP1P3, LOC100506207, and MIS18BP1/LINC00871. Combining data with a prior GWAS for rotator cuff tears in a meta-analysis resulted in the identification of an additional 7 loci: SLC39A8/UBE2D3, C5orf63, ASTN2, STK24, FRMPD4, ACOT9/SAT1, and LINC00890/ALG13. Many of the identified loci have known biologic functions or prior associations with diseases, suggesting possible biologic pathways leading to rotator cuff disease. RNA sequencing experiments show that expression of STK24 increases whereas expression of SAT1 and UBE2D3 decreases following rotator cuff tearing. Two SNPs previously reported to show an association with shoulder impingement from a prior UKB GWAS were not validated in our study. CONCLUSION: This is the first GWAS for shoulder impingement in which new data from UKB enabled the identification of 4 loci showing a genetic association. A meta-analysis with a prior GWAS for rotator cuff tearing identified an additional 7 loci. The known biologic roles of many of the 11 loci suggest plausible biologic mechanisms underlying the etiology of rotator cuff disease. The risk alleles from each of the genetic loci can be used to assess the risk for rotator cuff disease in individual patients, enabling preventative or restorative actions via personalized medicine.

Rotura del supraespinoso en paciente con pinzamiento subacromial crónico / Supraspinous rupture in patients with chronic subacromial impingement

En el espacio subacromial se desliza el manguito de los rotadores que cubren la cabeza humeral. La lesión de estos tendones, especialmente del supraespinoso, es origen de molestias que obligan a tratamientos prolongados, incluyendo el quirúrgico. El pinzamiento subacromial es un compromiso de la inserción del supraespinoso bajo el borde anterior del acromion y ligamento acromiocoracoideo. Hay tres estadios evolutivos: tendinopatía, rotura parcial y rotura transfixiante. Lesiones, que en un primer momento pueden ser pequeñas, con el esfuerzo diario aumentan y se agravan. Clínicamente el dolor suele exacerbarse con la elevación del brazo, de predominio nocturno, asociándose a debilidad y limitación del movimiento. El diagnóstico de rotura del supraespinoso es pasado por alto en Atención Primaria, y su retraso en el tratamiento tiene mal pronóstico. La radiología es normal inicialmente y el diagnóstico se confirma con ecografía, tomografía y resonancia. En pacientes mayores de 65 años suele optarse por un tratamiento conservador (AU)

In the subacromial space, the rotator cuff that covers the humeral head slides. Injury to these tendons, especially of the supraspinous one, is the origin of discomforts that require prolonged treatments, including surgery. Subacromial impingement is a compromise of the supraspinous insertion under the anterior border of the acromion and coracoacromial ligament. There are three evolutive stages: tendonitis, partial rupture and full-thickness rupture. Injuries which may be small in the beginning may increase and become worse with exercise. Clinically, the pain may worsen with elevation of the arm, with nighttime predominance, this being associated to weakness and movement limitation. Diagnosis of supraspinous rupture is overlooked in Primary Care and delay in its treatment has a poor prognosis. The x-ray is normal initially and diagnosis is confirmed with ultrasonography, tomography and resonance. Conservative treatment should be chosen in patients over 65 years (AU)