MMP20 Single-nucleotide Polymorphisms Correlate With Susceptibility To Alcohol-induced Osteonecrosis Of The Femoral Head In Chinese Males

Objective: Alcohol-induced osteonecrosis of the femoral head(ONFH)is a refractory orthopaedic disease caused by the interaction of genetic and environmental factors.Once it occurs,it will seriously affect the quality of life of patients.At present,the research suggests that the occurrence and development of alcohol osteonecrosis is a complex multi-gene,multi-factor,multi-link long-term interaction process.The genetic background of an individual plays an important role in determining the susceptibility of alcohol osteonecrosis,and this genetic background is mainly manifested in single nucleotide polymorphisms(SNPs)in the population.The study found that the genetic variation of the matrix metalloproteinase(MMP)system is related to the occurrence and development of ONFH.The aim of this study was to evaluate whether the MMP20 gene polymorphism in Chinese Han males is related to the genetic susceptibility of alcohol osteonecrosis,and to further screen out the susceptibility genes associated with the risk of osteonecrosis.This will provide a profound theoretical basis for understanding the causes of alcohol osteolyremia in future clinical studies,predicting the risk of onset,identifying high-risk groups,and reducing the incidence.).Methods: In this study,a candidate-gene case-control study strategy was used to collect 299 blood samples from patients diagnosed with osteonecrosis from September 2014 to January 2016,and 197 blood samples of healthy men who were examined at the hospital’s physical examination center during the same period.Genomic DNA of peripheral blood was extracted using the GoldMag-Mini Whole Blood Genomic DNA Purification Kit.The typing of 14 SNPs locus on the selected MMP20 gene were typed using the MassARRAY typing technique.Data management and analysis use SPSS software package 19.0,SNPstats,and SHEsis software.The effects of MMP20 gene polymorphism on the occurrence of alcoholic ONFH were evaluated by allelic model analysis,genotypic model analysis and haplotype analysis,and odds ratios(ORs)and 95% confidence intervals(CIs)were calculated.Results: By allele model analysis,the minimal alleles at locus rs10895322,rs1784424,rs3781788 andrs1573954 on MMP20 gene were associated with an increased risk of alcohol osteonecrosis(rs10895322G/A,OR = 1.422,95% CI = 1.069 – 1.892,P = 0.015;rs1784424T/G,OR =1.368,95% CI = 1.059 – 1.767,P = 0.016;rs3781788T/C,OR = 1.345,95% CI = 1.031 –1.755,P = 0.029;rs1573954C/T,OR = 1.328,95% CI = 1.028 – 1.716,P = 0.030).Under the logistic regression model and genetic model analysis,a total of 9 SNPs locus on MMP20 gene were associated with the occurrence of alcoholic osteonecrosis: two protective SNPs locus(rs1711423,rs1784418)and 7 high-risk SNPs locus(rs10895322,rs1784424,rs3781788,rs7126560,rs1573954,rs1711399,rs2292730).Finally,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).Conclusion: Our data first verify that MMP20 gene polymorphisms may correlate to alcohol-induced ONFH predisposition in Chinese Han males.These results are supposed to facilitate the ONFH genetic research.