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Association between vascular endothelial growth factor gene polymorphisms and the risk of osteonecrosis of the femoral head: Systematic review.

ABSTRACT: Emerging evidence has shown that vascular endothelial growth factor (VEGF) gene polymorphisms are the key initiators that regulate the expression of the VEGF protein, which has a vital role in osteonecrosis of the femoral head (ONFH). The aim of the present study was to investigate whether polymorphisms of the VEGF genes are associated with the occurrence of ONFH. A comprehensive search was performed on MEDLINE, Embase, Web of Science and China National Knowledge Infrastructure databases before June 2015. Meta-analyses were carried out for the VEGF gene -634G/C polymorphisms (single-nucleotide polymorphism with 3 eligible studies). The pooled odds ratios with 95% confidence intervals (CIs) were used to evaluate the strength of the association. All the eligible studies, involving 1,564 individuals, were identified. According to the inclusion criteria, 3 case-control studies were finally included in the meta-analysis. The present meta-analysis indicates that the VEGF gene -634G/C polymorphism [CC+GC vs. GG: Response rate (RR)=0.79; 95% CI, 0.67-0.92; GG vs. GC: RR=0.83; 95% CI, 0.72-0.97; GG vs. CC: RR=0.82; 95% CI, 0.72-0.93] is associated with the occurrence of ONFH, and the association with the male subgroup (RR=0.78; 95% CI, 0.65-0.94; P=0.009) is more evident. In conclusion, the present meta-analysis suggests that the VEGF gene -634G/C polymorphism has a significant association with ONFH occurrence among the investigated patients (P<0.01).

SUBMITTER: Hong GJ

PROVIDER: S-EPMC4726911 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Significant association between RETN genetic polymorphisms and alcohol-induced osteonecrosis of femoral head.

Project description:BackgroundAlcohol-induced osteonecrosis of femoral head (ONFH) is a complex disease and genetic factors are one of the causes. The purpose of this study is to investigate the effects of RETN (resistin; OMIM: 605565) and LDLR (low density lipoprotein receptor; OMIM: 606945) polymorphisms on the risk of alcohol-induced ONFH in Chinese Han population.MethodsA case-control study including 201 patients and 201 controls was designed. Seven single nucleotide polymorphisms (SNPs) in RETN gene and four SNPs in LDLR gene were genotyped using Agena MassARRAY platform. In allele model and genetic model, chi-square test and logistic regression were used to study the associations between these SNPs and ONFH susceptibility. In addition, the relationships between these SNPs, clinical phenotypes, and blood lipid level with one-way analysis of variance were analyzed.ResultsIn the allele model, rs7408174 and rs3745369 in RETN were associated with increased risk of alcohol-induced ONFH, whereas rs34861192 and rs3219175 in RETN showed reduced risk of alcohol-induced ONFH. In the genetic model, rs7408174 was associated with increased risk of alcohol-induced ONFH in dominant model and log-additive model. Rs3745369 showed an increased risk in codominant model, recessive model, and log-additive model. Rs34861192 showed a decreased risk in codominant model, dominant model, and log-additive model, and rs3219175 showed a decreased risk in dominant model and log-additive model. The rs3745368 in RETN was associated with the clinical stage of the disease.ConclusionThese results suggest that RETN genetic polymorphisms are associated with the susceptibility of alcohol-induced ONFH in Chinese Han population.

| S-EPMC6687866 | biostudies-literature

Genetic association of angiogenesis- and hypoxia-related gene polymorphisms with osteonecrosis of the femoral head.

Project description:Multiple factors have been implicated in the development of osteonecrosis of the femoral head (ONFH). In particular, non-traumatic ONFH is directly or indirectly related to injury of the vascular supply to the femoral head. Thus, hypoxia in the femoral head caused by impaired blood flow may be an important risk factor for ONFH. In this study, we investigated whether genetic variations of angiogenesis- and hypoxia-related genes contribute to an increased risk for the development of ONFH. Candidate genes were selected based on known hypoxia and angiogenesis pathways. An association study was performed using an Affymetrix Targeted Genotyping 3K Chip array with 460 ONFH patients and 300 control subjects. We showed that single nucleotide polymorphisms (SNPs) in the genes TF, VEGFC, IGFBP3, and ACE were associated with an increased risk of ONFH. On the other hand, SNPs in the KDR and NRP1 genes were associated with protection against ONFH. The most important finding was that one SNP (rs2453839) in the IGFBP3 gene was significantly associated with a higher risk of ONFH (P=0.0061, OR 7.74). In subgroup analysis, most candidate gene variations that were associated with ONFH occurred in the idiopathic subgroup. Among other SNPs, ACE SNPs were associated with steroid-induced ONFH (P=0.0018-0.0037, OR>3). Collectively, our findings suggest that genetic variations in angiogenesis- and hypoxia-related genes may help to identify susceptibility factors for the development of ONFH in the Korean population.

| S-EPMC2877256 | biostudies-literature

The genetic association between PON1 polymorphisms and osteonecrosis of femoral head: A case-control study.

Project description:The purpose of this study was to investigate the relationship between Paraoxonase-1 (PON1) gene rs662, rs854555 polymorphisms and osteonecrosis of the femoral head (ONFH) in Han population, northern China.Polymerase chain reaction-restriction fragment length polymorphism was used to determine genotypes of PON1 polymorphisms in 84 patients with ONFH and 96 healthy persons. χ test was used to compare distribution differences of genotype, allele, and haplotype between the case and control groups. The odds ratio (OR) and 95% confidence interval (CI) were calculated to reveal the effects of PON1 polymorphisms on risk of ONFH, and the results were adjusted using logistic regression analysis. The linkage disequilibrium and haplotype analysis were performed with haploview software.That people carrying AA genotype of rs662 were easier to be attacked by ONFH than GG genotype carriers (OR = 2.53, 95% CI = 1.05-6.07, P = .038). Meanwhile, the frequency of A allele in the case group was significantly higher than the controls and it was a risk factor for ONFH (OR = 1.56, 95% CI = 1.03-2.38, P = .038). The A-A haplotype frequency of rs854555-rs662 in PON1 was significantly correlated to the increased susceptibility to ONFH (OR = 2.74, 95% CI = 1.28-5.84).The rs662 polymorphism in PON1 may be associated with ONFH susceptibility, but not rs854555 in Han population, northern China. Additionally, haplotype is also a nonignorable risk factor.

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Association of Specific Genetic Polymorphisms with Atraumatic Osteonecrosis of the Femoral Head: A Narrative Review.

Project description:IntroductionAtraumatic ONFH is one of the leading cause of hip morbidity in the working-age group. It is a multi-factorial disease whose root cause can be attributed to single-nucleotide polymorphism. Identifying such polymorphisms could pave the way for new modalities of treatment for ONFH.MethodologyTwo databases were electronically searched for relevant articles. The articles were screened through titles, abstract and full texts to include the relevant studies. A secondary search was done through the reference list of selected articles.ResultsA total of 52 studies were included among the 181 hits. All 181 were case-control studies. Summary of these studies identifies multiple SNPs which can cause ONFH. There were 117 SNPs in all 181 studies, of which 92 were associated with the causation of ONFH and 25 were protective against ONFH.ConclusionSNPs play an essential role in causing atraumatic ONFH. Identification of SNP that contribute to causing ONFH may help reduce the disease burden by early identification, diagnosis and treatment, including targeted gene therapy.

| S-EPMC9043172 | biostudies-literature

Association of vascular endothelial growth factor polymorphisms with asthma in Tunisian children.

Project description:BACKGROUND:Previous studies demonstrated that the vascular endothelial growth factor (VEGF) was being implicated in the airways inflammation and remodeling process in patients with asthma. AIMS:We explored the relationship of three polymorphisms in the VEGF gene with asthma in both case control and family studies. METHODS:We Genotyped a total of 210 children with asthma, 224 unrelated controls and 160 parents for the +936 C >T (rs3025039), -634 G > C (rs2010963) and -2549 -2567 del 18 of the VEGF promoter region. The Mutations were identified with polymerase chain reaction followed by restriction fragment length polymorphism (RFLP) analysis for the +936 C > T, and -634 G > C polymorphisms. RESULTS:Of the three polymorphisms studied, a borderline association with asthma was found for the G allele in the -634 G > C polymorphism (p = 0.059). No Statistically significant differences were observed for both +936 C > T, and -2549 -2567 del 18 polymorphisms between asthmatic patients and controls, considering either allelic or genotypic frequencies. The distribution of genotypes according to the severity status revealed a significant differences for the +936 C > T, and -2549 -2567 del 18 polymorphisms. In addition, association was found with the haplotypes inferred by the three polymorphisms and asthma susceptibility. CONCLUSION:We suggest that VEGF Gene polymorphisms can be implicated in asthma.

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Association between vascular endothelial growth factor gene polymorphisms and bladder cancer risk.

Project description:Vascular endothelial growth factor (VEGF) gene polymorphisms are associated with susceptibility to a number of cancers. The present case-controlled study aimed to investigate the correlation between VEGF gene polymorphisms and the risk of bladder cancer. The effects of VEGF polymorphisms were investigated in patients with bladder cancer and healthy controls in our hospital between May, 2008 and May, 2013. Peripheral blood samples were obtained from 480 patients with bladder cancer and 420 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism technique was used to detect three VEGF gene polymorphisms (rs3025039 C/T, rs833052 C/A and rs1570360 G/A) in these subjects. The genotype and allele frequencies were also investigated in order to determine their association with stage, grade and histological type of bladder cancer, as well as smoking status. Our results suggested that the frequency of the rs833052 AA genotype was significantly higher in patients with bladder cancer [odds ratio (OR)=1.75; 95% confidence interval (CI): 1.05-2.92; P=0.03] compared to that in healthy controls. There was no significant correlation between the rs833052 AA genotype and bladder cancer stage, grade or histological type, whereas smoking was identified as a risk factor for bladder cancer in the included patients (OR=1.48; 95% CI: 1.13-1.93; P=0.004). The rs3025039 and rs1570360 gene polymorphisms were not found to be correlated with the risk of bladder cancer or its progression. In conclusion, our results suggested that the VEGF rs833052 C/A polymorphism may be associated with a modest increase in the risk of bladder cancer in Chinese individuals.

| S-EPMC4051574 | biostudies-literature

Association between <i>MMP-3</i> polymorphisms among Chinese patients with osteonecrosis of the femoral head.

Project description:Many potential causative factors are related to the initiation and progression of osteonecrosis of the femoral head (ONFH). The matrix metalloproteinase/tissue inhibitor of metalloproteinases (MMPs/TIMPs) system was found to play a significant role in the development of ONFH. The aim of this study is to investigate the association between polymorphisms of MMP-3 and ONFH in the Chinese population. We selected 8 single-nucleotide polymorphisms (SNPs) in 2 genes selected from the MMPs/TIMPs system in a case-control study with 585 cases of ONFH and 507 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi-squared test, genetic model analysis, haplotype analysis, and stratification analysis. We found that the minor allele of rs650108 and rs522616 (p<0.05) was assumed a risk allele compared to the wild-type allele. In the genetic model analysis, We observed two susceptibility SNPs additionally: rs650108, dominant model analyses (with adjustment: OR=0.73; 95%CI 0.56-0.95; p=0.017) and additive model analyses (with adjustment: OR=0.83; 95%CI 0.70-0.99; p=0.044); and rs522616 recessive model analyses (with adjustment: OR=1.52; 95%CI 1.07-2.14; p=0.018) and additive model analyses (with adjustment: OR=1.21; 95% CI 1.02-1.44; p=0.033). Our results verify that genetic variants of MMP3 contribute to ONFH susceptibility in the population of northern China. In addition, we found that gender differences might interact with MMP3 polymorphisms to contribute to the overall susceptibility to ONFH.

| S-EPMC5752487 | biostudies-literature

Association of polymorphisms in the Interleukin 23 receptor gene with osteonecrosis of femoral head in Korean population.

Project description:Osteonecrosis of the femoral head (ONFH) is known as death of the cellular portion of the femoral head due to an interruption in the vascular supply. The underlying pathophysiology regarding bone cell death remains uncertain. Recently, several studies have shown that autoimmune disorders were related to the development of osteonecrosis. This study investigated the genetic effects of Interleukin 23 receptor (IL23R) polymorphisms regarding the risk of ONFH. Ten SNPs were selected and genotyped in 443 ONFH patients and 273 control subjects in order to perform the genetic association analysis. It was found that polymorphisms of the IL23R gene (rs4655686, rs1569922 and rs7539625) were significantly associated with an increased risk of ONFH (P values; 0.0198-0.0447, OR; 1.30-1.49). Particularly, a stratified analysis based on etiology (alcohol, steroid or idiopathic) showed that the associations between these polymorphisms and ONFH were most significant in idiopathic ONFH patients (P values; 0.0001-0.0150, OR; 1.45-2.17). These results suggest that IL23R polymorphisms may play an important role in the development of ONFH.

| S-EPMC2679277 | biostudies-literature

Single Nucleotide Polymorphisms Other Than Factor V Leiden are Associated with Coagulopathy and Osteonecrosis of the Femoral Head in Chinese Patients

Project description:Single nucleotide polymorphisms (SNPs) of factor V Leiden have been associated with osteonecrosis of the femoral head (ONFH) in Caucasians but remains controversial in Asians. We used an SNP microarray to screen 55 loci of factor V gene in patients with ONFH of Chinese. Significantly different candidate SNPs at 14 loci were analyzed in 146 patients and 116 healthy controls using MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry and gene sequencing. The factor V Leiden (rs6025) was not found in all participants. Six SNP loci (rs9332595, rs6020, rs9332647, rs3766110, rs10919186, and rs12040141) were confirmed with significant differences in patients but not in controls. The rs6020 G-to-A polymorphism was found in 88.9% of the patients. In addition, a high percentage (84.7%) of the patients had an abnormal coagulation profile that included hyperfibrinogen, elevated fibrinogen degradation products, elevated D-dimer, abnormal protein S, abnormal protein C, or a decrease in anti-thrombin III. Patients with the rs6020 G-to-A polymorphism (mutation) had a higher risk (odds ratio: 4.33; 95% confidence interval: 1.36-13.76) of having coagulation abnormalities than did those without the mutation (wild-type) (p = 0.008). Our findings suggested that the rs6020 polymorphism might be the genetic trait that accounts for the higher prevalence of ONFH in the Chinese population than in Westerners. Exposure to risk factors such as alcohol and steroids in patients with the rs6020 polymorphism causes coagulation abnormalities and, subsequently, thromboembolisms in the femoral head.

2014-07-28 | GSE58951 | GEO

Endothelial nitric oxide synthase gene polymorphisms and the risk of osteonecrosis of the femoral head in systemic lupus erythematosus.

Project description:PURPOSE: Nitric oxide (NO), a short-lived gaseous free radical, is a potent mediator of biological responses involved in the pathogenesis of autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Nitric oxide also serves as an important signal in physiological processes, including angiogenesis, thrombosis, and bone turnover, which are known to be related to the pathogenesis of osteonecrosis. We investigated whether NOS3 gene polymorphisms are associated with risk of osteonecrosis of the femoral head (ONFH). METHODS: Five polymorphisms in the NOS3 gene were genotyped using TaqMan assays in 306 controls, 150 SLE patients, and 50 SLE patients with ONFH (SLE_ONFH). RESULTS: We found that Asp258Asp and Glu298Asp (G894T) polymorphisms in the NOS3 gene were significantly associated with risk of ONFH. Additionally, we calculated haplotype frequencies of a linkage disequilibrium (LD) block in NOS3 (rs1799983 - rs1800780) and tested for haplotype associations. The haplotypes G-A and T-A showed significant protective (P = 1.6 × 10(-3); OR 0.39, 95 % confidence intervals (CI) 0.22-0.7) and increased risk (P = 2.0 x 10(-5)-6.0 x 10(-4); OR 3.17-3.73) effects for ONFH, respectively. CONCLUSIONS: These results suggest that exonic NOS3 polymorphisms may increase the risk of ONFH in Korean SLE patients.

| S-EPMC3824903 | biostudies-literature

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