Wang Yuan, Yang Xuejun, Shi Jianping, Zhao Yan, Pan Linlin, Zhou Jinqiu, Wang Guoqiang, Wang Jianzhong
Department of Orthopedics, the People's Hospital of Manzhouli City, Manzhouli 021400, Inner Mongolia, China.
Department of Orthopedics, the Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia, China.
Oncotarget. 2017 May 16;8(20):33770-33778. doi: 10.18632/oncotarget.16809.
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.
In 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.
We 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).
This 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.
先前许多报道证实，多个基因的常见变异在股骨头坏死（ONFH）发病中起关键作用。我们推测，一氧化氮合酶3（NOS3）、ATP结合盒转运蛋白B1（ABCB1）和白细胞介素23受体（IL23R）基因多态性与酒精敏感性个体差异及酒精性ONFH的发生发展有关。
在这项病例对照研究中，我们评估了中国汉族人群中三个基因的8个单核苷酸多态性（SNP），包括355例男性病例和355例健康男性对照。这些SNP通过Sequenom MassARRAY RS1000进行基因分型。采用χ2检验和遗传模型分析确定它们与酒精性ONFH易感性的关系。
年龄校正后，我们发现三个基因中的4个SNP（rs743506、rs3918184、rs13233308和rs6693831）与酒精性ONFH易感性相关。NOS3基因中rs743506的基因型“G/A”在基因型（P = 0.003）、显性（P = 0.048）、隐性（P = 0.005）和加性模型（P = 0.006）中作为危险因素；NOS3基因中rs3918184的基因型“T/C”在基因型（P = 0.012）和隐性模型（P = 0.009）中作为危险因素；ABCB1基因中rs13233308的基因型“T/C”在基因型（P = 0.038）和加性模型（P = 0.041）中作为危险因素；IL23R基因中rs6693831的基因型“T/C”在基因型模型中作为保护因素（P = 0.046）。
本研究为中国男性酒精性ONFH的三个易感基因（NOS3、ABCB1和IL23R）提供了证据，它们的多态性可能与酒精性ONFH风险相关。
