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20 May 2019 : Laboratory Research  

MMP20 Single-Nucleotide Polymorphisms Correlate with Susceptibility to Alcohol-Induced Osteonecrosis of the Femoral Head in Chinese Males

Feimeng An12E, Jieli Du3E, Jiaqi Wang12B, Liang Zhao3C, Chao Ma2F, Jian Zhao2B, Jianzhong Wang2AG*

DOI: 10.12659/MSM.913918

Med Sci Monit 2019; 25:3750-3761

Abstract

BACKGROUND: Alcohol-induced osteonecrosis of the femoral head (ONFH) is caused by the interaction of genetic and environmental factors. Genetic variations of matrix metalloproteinase (MMP) system are associated with ONFH development and progression. In this study, we aimed to evaluate the relationships between MMP20 gene polymorphisms and the risk of alcohol-induced ONFH in Chinese Han males.

MATERIAL AND METHODS: In this case-control study, genotypes of 14 selected SNPs in the MMP20 gene were assayed using MassARRAY in 299 male cases with alcohol-induced ONFH and in 197 healthy males. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the influence of gene polymorphism on occurrence of alcohol-induced ONFH by allelic model analysis, genotype model analysis and haplotype analysis.

RESULTS: After allelic model analysis, the minimum alleles of rs10895322, rs1784424, rs3781788, and rs1573954 correlated with an increased risk of alcohol-induced ONFH (P<0.05). Genetic model analysis revealed significant associations of 9 SNPs with alcohol-induced ONFH occurrence even after adjustment for age (P<0.05): 2 protective SNPs (rs1711423 and rs1784418) and 7 high-risk SNPs (rs10895322, rs1784424, rs3781788, rs7126560, rs1573954, rs1711399, and rs2292730). Moreover, 8 SNPs showed a statistically significant association with different clinical phenotypes (P<0.05). Beyond that, haplotype “CGGTTCCA” in MMP20 was discovered to correlate with a 1.63-fold increased risk of alcohol-induced ONFH (OR: 1.63, 95% CI: 1.15–2.30, P=0.0058).

CONCLUSIONS: Our data sheds new light on the associations of MMP20 gene polymorphisms with alcohol-induced ONFH predisposition in Chinese Han males.

Keywords: Genetic Association Studies, Matrix Metalloproteinase 20, osteonecrosis, Polymorphism, Genetic, Adult, Alcohol Drinking, Alleles, Asians, Case-Control Studies, China, Femur Head, Femur Head Necrosis, Gene Frequency, Genetic Predisposition to Disease, Genotype, Haplotypes, Linkage Disequilibrium, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750