Genetic polymorphisms in plasminogen activator inhibitor-1 predict susceptibility to steroid-induced osteonecrosis of the femoral head in Chinese population

Yanqiong Zhang,Xiangying Kong,Weiheng Chen,Shangzhu Li,Na Lin,Rongtian Wang,Zhiyao Wang

doi:10.1186/1746-1596-8-169

Abstract

BackgroundSteroid usage has been considered as a leading cause of non-traumatic osteonecrosis of the femoral head (ONFH), which is involved in hypo-fibrinolysis and blood supply interruption. Genetic polymorphisms in plasminogen activator inhibitor-1 (PAI-1) have been demonstrated to be associated with ONFH risk in several populations. However, this relationship has not been established in Chinese population. The aim of this study was to investigate the association of PAI-1 gene polymorphisms with steroid-induced ONFH in a large cohort of Chinese population.MethodsA case–control study was conducted, which included 94 and 106 unrelated patients after steroid administration recruited from 14 provinces in China, respectively. Two SNPs (rs11178 and rs2227631) within PAI-1 were genotyped using Sequenom MassARRAY system.Resultsrs2227631 SNP was significantly associated with steroid-induced ONFH group in codominant (P = 0.04) and recessive (P = 0.02) models. However, there were no differences found in genotype frequencies of rs11178 SNP between controls and patients with steroid-induced ONFH (all P > 0.05).ConclusionsOur data offer the convincing evidence for the first time that rs2227631 SNP of PAI-1 may be associated with the risk of steroid-induced ONFH, suggesting that the genetic variations of this gene may play an important role in the disease development.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1569909986109783.

Highlights

Non-traumatic osteonecrosis of femoral head (ONFH) represents an intractable bone disease, pathophysiologically characterized by progressive collapse of the femoral head because of a disturbance in the supply of blood and anomalies in the fibrinolytic system [1,2]
Asano et al [21] using Japanese population suggested that plasma plasminogen activator inhibitor-1 (PAI-1) levels were highest in ONFH patients with the 4G/4G genotype, but that the incidence of ONFH was not related to this genotype. These findings indicated that the genetic polymorphisms within the Plasminogen activator inhibitor (PAI)-1 gene may play an important role in the development of ONFH
The steroid-induced ONFH patients were more likely in men subgroup, and to have a smaller BMI when compared to the controls

Summary

Introduction

Non-traumatic osteonecrosis of femoral head (ONFH) represents an intractable bone disease, pathophysiologically characterized by progressive collapse of the femoral head because of a disturbance in the supply of blood and anomalies in the fibrinolytic system [1,2]. Since this ischemic necrosis of the femoral head and deterioration of hip joint function may significantly affect patient quality of life, it is urgent to clarify the pathogenic mechanisms regarding this disease. Genetic polymorphisms in plasminogen activator inhibitor-1 (PAI-1) have been demonstrated to be associated with ONFH risk in several populations. The aim of this study was to investigate the association of PAI-1 gene polymorphisms with steroid-induced ONFH in a large cohort of Chinese population

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