Relationship of common variants in MPP7, TIMP2 and CASP8 genes with the risk of chronic achilles tendinopathy

Previous etiologic studies have indicated that both environmental and genetic factors play important roles in the occurrence and development of chronic Achilles tendinopathy (AT). A recent study documented the results of the largest genome-wide association study for chronic AT to date, indicating that MPP7, TIMP2 and CASP8 may be involved in the occurrence and development of chronic AT. In this study, we aimed to investigate whether MPP7, TIMP2 and CASP8 were associated with susceptibility to chronic AP in a Han Chinese population. A total of 3,680 study subjects comprised 1,288 chronic AT cases, and 2,392 healthy controls were recruited. Forty-four tag SNPs (7 from CASP8, 20 from MPP7, and 17 from TIMP2) were genotyped in the study. Genetic association analyses were performed at both single marker and haplotype levels. Functional consequences of significant SNPs were examined in the RegulomeDB and GTEx databases. Two SNPs, SNP rs1937810 (OR [95%CI] = 1.20 [1.09–1.32], χ(2) = 13.50, P = 0.0002) in MPP7 and rs4789932 (OR [95%CI] = 1.24 [1.12–1.37], χ(2) = 17.98, P = 2.23 × 10(−5)) in TIMP2, were significantly associated with chronic AT. Significant eQTL signals for SNP rs4789932 on TIMP2 were identified in human heart and artery tissues. Our results provide further supportive evidence for the association of the TIMP2 and MPP7 genes with chronic AT, which supports important roles for TIMP2 and MPP7 in the etiology of chronic AT, adding to the current understanding of the susceptibility of chronic AT.