Abstract

BackgroundCommon variants of multiple genes played a crucial role in osteonecrosis of the femoral head (ONFH) onset which was proved by many previous reports. We hypothesized that polymorphisms in NOS3, ABCB1 and IL23R were related to individual differences in alcohol sensitivity and the development of alcohol-induced ONFH.MethodsIn this case-control study, we evaluated 8 SNPs in three genes in the Chinese Han population including 355 male cases and 355 healthy male controls. These SNPs were genotyped by Sequenom MassARRAY RS1000. To identify their relationship with alcohol-induced ONFH susceptibility using χ2 test and genetic model analysis.ResultsWe found an association with alcohol-induced ONFH susceptibility for 4 SNPs (rs743506, rs3918184, rs13233308 and rs6693831) in three genes after adjusted by age. The genotype “G/A” of rs743506 in NOS3 gene acts as a risk factor in genotype (P = 0.003), dominant (P = 0.048), recessive (P = 0.005) and additive model(P = 0.006); The genotype “T/C” of rs3918184 in NOS3 gene acts as a risk factor in genotype (P = 0.012) and recessive model (P = 0.009); The genotype “T/C” of rs13233308 in ABCB1 gene acts as a risk factor in genotype (P = 0.038) and additive model(P = 0.041); The genotype “T/C” of rs6693831 in IL23R gene acts as a protective factor in genotype model (P = 0.046).ConclusionsThis study provides evidence for three alcohol-induced ONFH susceptibility genes (NOS3, ABCB1 and IL23R) in Chinese males and polymorphisms of them may be associated with alcohol-induced ONFH risk.

Highlights

  • Osteonecrosis of the femoral head (ONFH) indicates a debilitating disorder that the bone collapses, happening in a special anatomical site of femoral head and resulting in osteocyte death [1, 2]

  • This study provides evidence for three alcohol-induced ONFH susceptibility genes (NOS3, adenosine triphosphate-binding cassette B1 (ABCB1) and IL23R) in Chinese males and polymorphisms of them may be associated with alcohol-induced ONFH risk

  • Eight single nucleotide polymorphisms (SNPs) loci(rs6693831, rs790631, rs4148749, rs10808072, rs13233308, rs3918227, rs3918184 and rs743506) in the nitric oxide synthase 3 (NOS3), ABCB1 and IL23R were evaluated in this study

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Summary

Introduction

Osteonecrosis of the femoral head (ONFH) indicates a debilitating disorder that the bone collapses, happening in a special anatomical site of femoral head and resulting in osteocyte death [1, 2]. It mainly affects younger males who is between 30 and 50 years old. The seventy-five to ninety percent cases of ONFH have been associated with various risk factors, involving alcohol www.impactjournals.com/oncotarget Parameters Cases Controls Age [mean±SD] 44.91 ± 9.85 46.02 ± 9.61 Sex [male] BMI (kg/m2) ≥25 < 25. Common variants of multiple genes played a crucial role in osteonecrosis of the femoral head (ONFH) onset which was proved by many previous reports. We hypothesized that polymorphisms in NOS3, ABCB1 and IL23R were related to individual differences in alcohol sensitivity and the development of alcohol-induced ONFH

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