RESUMEN
Alcohol-induced osteonecrosis of femoral head (ONFH) is one of the most important pathogenesis of nontraumatic ONFH. However, its pathogenesis mechanism is still unknown. Osteoprotegerin (OPG) has been implicated in multiple functions including blocking osteoclast maturation, controlling vascular calcifications, promoting tumour growth and metastasis. This study is focussed on OPG gene polymorphisms associated with alcohol-induced ONFH. A total of 509 participants (209 patients and 300 normal individuals) were recruited, and we selected 13 single-nucleotide polymorphisms (SNPs) to evaluate the association between genetic susceptibility variants and alcohol-induced ONFH by using the χ2 test and genetic model analysis. Overall, OPG SNPs (rs1485286, rs1032128 and rs11573828) were confirmed the strongest increasing risks on alcohol-induced osteoporosis of femoral head in recessive model (rs1485286: OR, 1.71; 95% CI, 1.07-2.73; P = 0.025 for T/T); (rs1032128: OR, 1.73; 95% CI, 1.08- 2.77; P = 0.022 for G/G); (rs11573828: OR, 3.89; 95% CI, 1.02- 14.85; P = 0.033 for T/T). SNP rs11573856 was considered as a protective effect to the occurrence of alcohol-induced ONFH, while adjusted for age and gender in dominant and log-additive models (rs11573856: adjusted OR, 0.60; 95% CI, 0.37- 0.96; P = 0.033 for G/A- A/A); (rs11573856: adjusted OR, 0.63; 95% CI, 0.41- 0.96; P = 0.042). We conclude that OPG gene polymorphisms were associated with the occurrence of alcohol-induced ONFH.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Necrosis de la Cabeza Femoral/etiología , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Osteoprotegerina/genética , Polimorfismo de Nucleótido Simple , Alelos , Estudios de Casos y Controles , China/epidemiología , Femenino , Necrosis de la Cabeza Femoral/epidemiología , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Oportunidad RelativaRESUMEN
Alcohol-induced osteonecrosis of the femoral head (ONFH) is an important pathogenesis of nontraumatic ONFH. However, the mechanisms of the pathogenesis are still unknown. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) have been implicated in multiple functions including blocking osteoclast maturation, controlling vascular calcifications, and promoting tumor growth and metastasis. The purpose of this article was to explore the association between OPG and RANKL gene variants and alcohol-induced ONFH. Six hundred seventy male subjects (335 patients and 335 normal individuals) were enrolled in our study. We selected 24 single-nucleotide polymorphisms (SNPs) to evaluate the association between genetic susceptibility variants and alcohol-induced ONFH using the chi-square test and gene model analysis. Overall, the OPG SNPs (rs1032128 and rs11573828) were associated with the strongest increased risk of alcohol-induced ONFH in the recessive model (rs1032128: odds ratio [OR] 1.49, 95% confidence interval [CI] 1.00-2.22, Pâ=â0.04 for G/A; rs11573828: OR 3.32, 95% CI 1.07-10.30, Pâ=â0.03 for T/C). The RANKL SNP rs2200287 was also an increased risk factor (OR 3.65, 95% CI 1.53-8.47, Pâ=â0.003 for T/C) in the recessive model. The rs11573856, rs3134056, and rs1564861 SNPs were considered protective factors for alcohol-induced ONFH. We concluded that OPG and RANKL polymorphisms were associated with the occurrence of alcohol-induced ONFH.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , ADN/genética , Necrosis de la Cabeza Femoral/genética , Osteoprotegerina/genética , Polimorfismo de Nucleótido Simple , Ligando RANK/genética , Adulto , Consumo de Bebidas Alcohólicas/genética , Consumo de Bebidas Alcohólicas/metabolismo , China/epidemiología , Femenino , Necrosis de la Cabeza Femoral/epidemiología , Necrosis de la Cabeza Femoral/etiología , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Osteoprotegerina/metabolismo , Ligando RANK/metabolismo , Estudios Retrospectivos , Adulto JovenRESUMEN
Polymorphisms of apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1) gene and ApoB/ApoA1 Ratio were associated with lipid metabolism disorders in previous reports. The aim of this study assess whether variation of ApoB, ApoA1 gene are associated or not with alcohol-induced osteonecrosis of femoral head (ONFH). In a case-control study, we genotyped 4 single-nucleotide polymorphisms (SNPs) in ApoB and ApoA1 genes in 209 alcohol-induced ONFH patients and 300 healthy control subjects in Han Chinese population using χ(2) test and genetic model analysis. The analysis revealed that the frequencies of ApoB and ApoA1 genotypes were significantly different in alcohol-induced ONFH patients than in controls. We identified rs1042034, rs676210 and rs673548 in ApoB gene were associated with decreased risk of alcohol-induced ONFH using recessive model analysis (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.19-0.99; P = 0.042), the OR, CI, P value of three SNPs were the same after adjusted for gender + age. We also identified rs632153 in ApoA1 gene was associated with increased risk of alcohol-induced ONFH using allele model (OR, 1.83; 95% CI, 1.16-2.88; P = 0.008) and log-additive model (adjusted OR, 1.77; 95% CI, 1.00-3.14; P = 0.046), analysis respectively. Haplotype analysis demonstrated no difference between ApoB and alcohol-induced ONFH. Polymorphisms of the ApoB and ApoA1 gene are associated with alcohol-induced ONFH in the Han Chinese population.