Single-nucleotide polymorphisms of MMP2 in MMP/TIMP pathways associated with the risk of alcohol-induced osteonecrosis of the femoral head in Chinese males

Abstract

The proportion of alcohol-induced osteonecrosis of the femoral head (ONFH) in all ONFH patients was 30.7%, with males prevailing among the ONFH patients in mainland China (70.1%). Matrix metalloproteinase 2 (MMP2), a member of the MMP gene family, encodes the enzyme MMP2, which can promote osteoclast migration, attachment, and bone matrix degradation. In this case–control study, we aimed to investigate the association between MMP2 and the alcohol-induced ONFH in Chinese males.In total, 299 patients with alcohol-induced ONFH and 396 healthy controls were recruited for a case–control association study. Five single-nucleotide polymorphisms within the MMP2 locus were genotyped and examined for their correlation with the risk of alcohol-induced ONFH and treatment response using Pearson χ2 test and unconditional logistic regression analysis. We identified 3 risk alleles for carriers: the allele “T” of rs243849 increased the risk of alcohol-induced ONFH in the allele model, the log-additive model without adjustment, and the log-additive model with adjustment for age. Conversely, the genotypes “CC” in rs7201 and “CC” in rs243832 decreased the risk of alcohol-induced ONFH, as revealed by the recessive model. After the Bonferroni multiple adjustment, no significant association was found. Furthermore, the haplotype analysis showed that the “TT” haplotype of MMP2 was more frequent among patients with alcohol-induced ONFH by unconditional logistic regression analysis adjusted for age.In conclusion, there may be an association between MMP2 and the risk of alcohol-induced ONFH in North-Chinese males. However, studies on larger populations are needed to confirm this hypothesis; these data may provide a theoretical foundation for future studies.

Stromal-Cell-Derived Factor (SDF) 1-Alpha Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Osteonecrosis of the Femoral Head

“…Although corticosteroid usage [5], alcohol consumption [6, 7], and trauma [8] have been identified as risk factors for ONFH, its pathogenesis remains poorly understood. Currently, surgical prevention is the conventional therapeutic strategy, which is invasive and may decrease the quality of life.…”

TIMP3 gene polymorphisms and relation to Ankylosing spondylitis susceptibility in Chinese Han population

“…TIMP3 gene belongs to the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the ECM (Okada et al, ; Yu et al, ). In the ECM, the N‐terminal of TIMP3 binds to the active site of matrix metalloproteinases (MMPs), thus preventing substrate recognition and inhibiting proteolytic enzymes such as MMP2.…”

Matrix metalloproteinase-2 gene polymorphisms are associated with ischemic stroke in a Hainan population

“…MMPs involve in many physiological processes, such as cell growth, proliferation, differentiation, migration, apoptosis, and cell interactions. [ 23 , 24 ] MMPs are secreted in the form of inactive proenzymes and obtain activity when they are cracked by extracellular proteinases. [ 25 , 26 ] A large number of studies have verified that the genetic polymorphisms within the MMP genes that alter expression levels of the enzymes, implying a possible role in IS development.…”