Genetic Association between Methylenetetrahydrofolate Reductase Gene Polymorphism and Risk of Osteonecrosis of the Femoral Head

Abstract

Background. Methylenetetrahydrofolate reductase (MTHFR) SNP rs1801133 has been frequently investigated in recent years. Relevant candidate gene association studies with this SNP and osteonecrosis of the femoral head (ONFH) reported conflicting results. Meta-analysis provides a method to combine these data and to determine the association in a larger sample size. Method. We conducted a systematic search to identify possible studies. Four pooled ORs (odds ratios, T versus C, TT versus CC, TT/CT versus CC, and TT versus CT/CC), along with 95% confidence interval (CI), were calculated to evaluate the association between SNP rs1801133 and ONFH susceptibility. Both fixed effects model and random effects model were used. Findings. We eventually included twelve studies in this analysis, with results showing no overall association between ONFH susceptibility and SNP rs1801133 (T versus C: OR = 1.15, 95% CI = 0.97–1.38; TT versus CC: OR = 1.15, 95% CI = 0.91–1.46; TT/CT versus CC: OR = 1.09, 95% CI = 0.95–1.25; and TT versus CT/CC: OR = 1.16, 95% CI = 0.93–1.45). When stratified based on ethnicity, the results were still not significant. Conclusion. Our findings are generally supportive of no association between MTHFR SNP rs1801133 and the etiology of ONFH.

Combination Analysis of NR3C1, MTHFR and IGFBP3 Gene Polymorphisms and DNA Methylation With Steroid-induced Osteonecrosis of the Femoral Head Risk in Chinese Han Population 

“…When ethnicity was strati ed, this meta-analysis provided no evidence of an association between rs1801133 polymorphism and ONFH. Twelve studies were included in the meta-analysis of Chai et al (2015). The results showed that there was no direct association between ONFH susceptibility and rs1801133 polymorphism.…”

“…Statistical analysis SPSS 24.0 (SPSS, Chicago, IL) was used for statistical analysis. The allele distribution was tested for Hardy-Weinberg equilibrium (HWE) by χ 2 . The ORs and 95% CI was determined by unconditional logistic regression analysis.…”

“…Mutations in the MTHFR gene signi cantly reduce the activity of the enzyme, resulting in elevated plasma homocysteine levels. Homocysteine can lead to vascular endothelial injury, thereby proliferating vascular endothelial cells, enhancing the coagulation activity of vascular walls, and leading to the formation of microvascular thrombosis (Chai et al 2015). In addition, homocysteine directly damages bone tissue by enhancing osteoclast production and activity (Koh et al 2006).…”

Association between NOS3 polymorphisms and osteonecrosis of the femoral head

“…With advancements in molecular techniques, genetic factors have been generally accepted to play critical roles in the etiology of non-trauma ONFH [8]. A variety of genes have been confirmed to be involved in ONFH pathogenesis, such as MTHFR, CYP3A4, CYP2D6, CYP2C19, ABCB1/MDR1, and nitric oxide synthase 3 (NOS3) gene [9][10][11][12].…”

Association of SREBP2 gene polymorphisms with the risk of osteonecrosis of the femoral head relates to gene expression and lipid metabolism disorders

“…The polymorphisms of multiple genes have been suggested to be associated with ONFH risk. These polymorphisms are thought to cause disequilibrium with other genes, affecting ONFH occurrence, or to play a synergistic role in the development of ONFH by interfering with the expression of other genes (3)(4)(5)(6) The ONFH patients often occur with a severe lipid metabolism disorder and the adipose accumulation in the impaired bone marrow cavity. Thus, lipid metabolism disorder has generally been regarded as a critical factor in ONFH pathogenesis, but the molecular mechanism of the adipose accumulation remains unclear.…”