Association Of Gene Polymorphism Of RETN And LDLR With Alcohol-Induced Osteonecrosis Of The Femoral Head

Objective: Alcohol-induced osteonecrosis of the femoral head(alcohol-induced ONFH)is a kind of lesion caused by various reasons such as defective femoral head blood supply,resulting in bone ischemia,necrosis,trabecular fracture,and femoral head collapse.The main clinical manifestations are hip pain,functional dysfunction,and limited movement.Osteonecrosis of the femoral head is a clinically complex disease,usually divided into two types: traumatic and non-traumatic.Alcohol-induced osteonecrosis of the femoral head is a non-traumatic ONFH,and alcohol consumption is an important pathogenic factor.However,clinical studies have found that only a part of drinkers suffer from alcohol-induced ONFH.Current studies suggest that individual genetic factors play an important role in the incidence of alcohol-induced ONFH.According to relevant literature reports,resistin encoded by human resistin gene(RETN;OMIM: 605565)affects bone metabolism in human body.In vitro studies have shown that it can promote bone remodeling,and both osteoclasts and osteoblasts express resistin.Low density lipoprotein receptor gene(LDLR;OMIM: 606945)plays an important role in regulating plasma cholesterol level,which is harmful to bone health when cholesterol metabolism is disordered.This experiment aims to explore whether there is a potential correlation between RETN gene and LDLR gene polymorphism and alcohol-induced ONFH in Chinese Han population.Methods: A case-control study was conducted to collect 201 blood samples of alcoholic ONFH from male Han population in northern China,and 201 blood samples from healthy male Han population in northern China matched with the age of the case group.Genomic DNA was extracted from the peripheral blood of the participants using the Gold Mag whole blood genomic DNA purification kit.Seven single nucleotide polymorphisms(SNPs)in the RETN gene and four SNPs in the LDLR gene were analyzed using the Agena Mass ARRAY platform.The Agena Mass ARRAY RS1000 was used for genotyping.The genotyping primers were designed with the Agena Mass ARRAY Assay Design 3.0 Software.Agena Typer 4.0 Software was used for managing the related data.T test,chi-square test,regression analysis and other statistical methods were carried out for data analysis by SPSS software package 19.0 software.Results: In the allele model,rs7408174(OR=1.43,95%CI:1.03-1.98,p=0.032)and rs3745369(OR=1.35,95%CI:1.01-1.81,p=0.045)in RETN were associated with increased risk of alcohol-induced ONFH,whereas rs34861192(OR=0.63,95%CI:0.43-0.92,p=0.016)and rs3219175(OR=0.67,95%CI:0.46-0.97;p=0.032)in RETN showed reduced risk of alcoholinduced ONFH.In the genetic model,rs7408174 was associated with increased risk of alcoholinduced ONFH in dominant(OR = 1.57,95% CI: 1.05-2.34,p = 0.028)model and log-additive(OR = 1.47,95% CI: 1.05-2.06,p = 0.024)model.Rs3745369 showed an increased risk in codominant model(OR = 2.50,95% CI: 1.28-4.90,p = 0.007),recessive model(OR = 2.55,95% CI: 1.35-4.81,p = 0.004)and log-additive model(OR = 1.36,95% CI: 1.01-1.82,p = 0.042).Rs34861192 showed a decreased risk in codominant model(OR = 0.62,95% CI: 0.39-0.96,p = 0.032),dominant model(OR = 0.59,95% CI: 0.38-0.91,p = 0.017)and log-additive model(OR = 0.61,95% CI: 0.41-0.90,p = 0.013),and rs3219175 showed a decreased risk in dominant model(OR = 0.64,95% CI: 0.42-0.97,p = 0.036)and log-additive model(OR = 0.65,95% CI: 0.44-0.95,p = 0.025).The rs3745368 in RETN was associated with the clinical stage of the disease(p=0.022).Conclusion: This study is the first to explore the association between RETN gene polymorphism and the genetic susceptibility to alcohol-induced ONFH in Chinese Han population.