scholarly journals Association of TIMP4 gene variants with steroid-induced osteonecrosis of the femoral head in the population of northern China

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6270
Author(s):  
Jiaqi Wang ◽  
Feimeng An ◽  
Yuju Cao ◽  
Hongyan Gao ◽  
Mingqi Sun ◽  
...  
Keyword(s):  
Femoral Head ◽  
Additive Model ◽  
Northern China ◽  
Additive Models ◽  
Gene Variants ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Link Type ◽  
Intravascular Thrombosis ◽  
Normal Individuals

BackgroundIn clinical treatment, the use of steroid hormones is an important etiological factor of non-traumatic osteonecrosis of the femoral head (ONFH) risk. As an endogenous inhibitor of matrix metalloproteinases (MMPs) in the extracellular matrix, the expression of tissue inhibitors of metalloprotease-4 (TIMP4) plays an essential role in cartilage and bone tissue damage and remodeling, vasculitis formation, intravascular thrombosis, and lipid metabolism.MethodsThis study aimed to detect the association between TIMP4 polymorphism and steroid-induced ONFH. We genotyped seven single-nucleotide polymorphisms (SNPs) in TIMP4 genes and analyzed the association with steroid-induced ONFH from 286 steroid-induced ONFH patients and 309 normal individuals.ResultsWe performed allelic model analysis and found that the minor alleles of five SNPs (rs99365,rs308952,rs3817004,rs2279750, andrs3755724) were associated with decreased steroid-induced ONFH (p = 0.02,p = 0.03,p = 0.04,p = 0.01,p = 0.04, respectively).rs2279750showed a significant association with decreased risk of steroid-induced ONFH in the Dominant and Log-additive models (p = 0.042,p = 0.028, respectively), andrs9935,rs30892, andrs3817004were associated with decreased risk in the Log-additive model (p = 0.038,p = 0.044,p = 0.042, respectively). In further stratification analysis, TIMP4 gene variants showed a significant association with steroid-induced ONFH in gender under the genotypes. Haplotype analysis also revealed that “TCAGAC” and “CCGGAA” sequences have protective effect on steroid-induced ONFH.ConclusionOur results indicate that five TIMP4 SNPs (rs99365,rs308952,rs3817004rs2279750, andrs3755724) are significantly associated with decreased risk of steroid-induced ONFH in the population of northern China.

scholarly journals Association of IGF1 single-nucleotide polymorphisms with myopia in Chinese children

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8436
Author(s):  
Tianyu Cheng ◽  
Jingjing Wang ◽  
Shuyu Xiong ◽  
Bo Zhang ◽  
Qiangqiang Li ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Chinese Population ◽  
Additive Models ◽  
Chinese Children ◽  
Nucleotide Polymorphisms ◽  
Chi Square ◽  
Single Nucleotide ◽  
Link Type ◽  
Polymerase Chain ◽  
And Gender

Purpose To investigate the association between insulin-like growth factor 1 (IGF1) single-nucleotide polymorphisms (SNPs) and myopia in a young Chinese population. Methods A total of 654 Chinese children aged 6–13 years from one primary school participated in our study and underwent a series of comprehensive ocular examinations, including cycloplegic refraction and measurements of axial length. Myopia was defined as a spherical equivalence (SE) ≤ −0.5 D in the worse eye. In total, six tagging SNPs of IGF1 were genotyped using the PCR-LDR (Polymerase Chain Reaction-Ligation Detection Reaction) method. We tested four different genetic modes (the allele, dominant, recessive, and additive models) of these SNPs and used multivariate logistic regression to calculate the effect of SNPs on myopia. In addition, we conducted a haplotype analysis with a variable-sized slide-window strategy. Results Overall, 281 myopic children and 373 non-myopic controls were included in the analysis. The SNP rs2162679 showed a statistical difference between the two groups in both the allele (p = 0.0474) and additive (p = 0.0497) models. After adjusting for age and gender, children with the genotype AA in the SNP rs2162679 had a higher risk of myopia than those with the genotype GG (OR = 2.219, 95% CI [1.218–4.039], p = 0.009). All haplotypes that varied significantly between the two groups contained the SNP rs2162679, and the four-SNP window rs5742653–rs2162679 had the lowest p value (Chi square = 5.768, p = 0.0163). However, after permutation tests, none of the associations remained statistically significant. Conclusion The SNP rs2162679 in IGF1 was associated with myopia in a young Chinese population. The G allele in the SNP rs2162679 may protect against myopia.

Abstract P103: Genome-Wide Study of Gene Variants Associated with Differential Event Reduction by Pravastatin Therapy

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Dov Shiffman ◽  
Stella Trompet ◽  
Judy Z Louie ◽  
Charles M Rowland ◽  
Joseph J Catanese ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Statin Therapy ◽  
Additive Model ◽  
The Elderly ◽  
Controlled Study ◽  
Gene Variants ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Genome Wide Study

BACKGROUND : Statin therapy reduces the risk of coronary heart disease (CHD); however, the variability in response to statin therapy is not well understood. We investigated the effect of genetic variation on the reduction of CHD events by pravastatin therapy. METHODS : We genotyped 682 CHD cases from CARE and 383 CHD cases from WOSCOPS, two randomized placebo-controlled studies of pravastatin using the Illumina OMNI1 bead array. Single nucleotide polymorphisms (SNPs) that were associated with differential CHD event reduction by pravastatin therapy were investigated in PROSPER, a randomized placebo-controlled study of pravastatin in the elderly. RESULTS : A combined case-only analysis of CARE and WOSCOPS identified 62 SNPs associated with differential event reduction by pravastatin therapy (P int <0.0001 for interaction between treatment and genotype in an additive model). We investigated 57 of these SNPs in PROSPER. In an analysis that included cases as well as non-cases of CARE, WOSCOPS, and PROSPER, we found that for an intronic SNP in DNAJC5B (rs13279522), CHD event reduction by pravastatin therapy according to genotype differed in all 3 studies: P int =0.001 in CARE, P int =0.01 in WOSCOPS, P int =0.002 in PROSPER, and P int =3X10 -7 in a combined analysis of CARE, WOSCOPS and PROSPER (Figure). CONCLUSIONS : We have identified a SNP that is associated with differential event reduction by pravastatin therapy in CARE, WOSCOPS, and PROSPER. This SNP merits investigation in additional randomized studies of pravastatin and other statins.

scholarly journals DPP4 rs16822665 and rs2268694 had Protective Effect on Osteonecrosis of the Femoral Head

2021 ◽  
Author(s):  
Chang Liu ◽  
Xuan Liu ◽  
Xiaolin Li
Keyword(s):  
Femoral Head ◽  
Additive Models ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Single Nucleotide ◽  
Gender Stratification ◽  
Risk Of Disease ◽  
Orthopedic Diseases ◽  
Stratified Analysis ◽  
The Relationship

Abstract Background: It is reported that DPP4 is associated with bone metabolism, osteoporosis and other orthopedic diseases, but the correlation between DPP4 and osteonecrosis of the femoral head (ONFH) is not clear. It was the purpose of this study that was to explore the relationship between DPP4 gene and ONFH.Methods: We genotyped four single nucleotide polymorphisms (SNPs) from DPP4 gene using the Agena MassARRAY platform. The association between DPP4 variants and ONFH susceptibility was assessed using odds ratio (OR) and 95% confidence intervals (CIs) via logistic regression. Results: The results showed that the allele C of rs16822665 was related to a lower risk of ONFH (OR = 0.76, 95%CI = 0.63-0.92, p = 0.006). In the case of stratified analysis, we found that rs16822665 could reduce the incidence of ONFH risk in four genetic models (dominant, codominant, log-additive, and recessive models) in drinkers and people age ≤51 years (p < 0.05). In gender stratification analysis, both rs2268694 and rs16822665 were contributed to bring down the risk of disease, which were mainly reflected in the codominant, dominant and log-additive models in female (p < 0.05). The subgroup analysis was conducted based on smokers revealing that rs2268894 was vitally correlated with a decreased risk of ONFH in the codominant (C vs. T: OR = 0.51, 95% CI: 0.34-0.76, p = 0.001), dominant (TC-CC vs. TT: OR = 0.53, 95% CI: 0.36-0.77, p = 0.001), and log-additive (OR = 0.65, 95% CI: 0.48-0.88, p = 0.006) models, while it was not found in the non-smokers.Conclusions: This finding provide evidence that DPP4 variants play a key role in the occurrence of ONFH among the Chinese Han population.

scholarly journals Association between Genetic Polymorphisms of MIR3142HG and the Risk of Steroid-Induced Osteonecrosis of the Femoral Head in the Population of Northern China

2021 ◽  
pp. 1-9
Author(s):  
Tiantian Wang ◽  
Huiqiang Wu ◽  
Menghu Sun ◽  
Tingting Liu ◽  
Feimeng An ◽  
...  
Keyword(s):  
Femoral Head ◽  
Protective Factor ◽  
Genetic Model ◽  
Additive Model ◽  
Northern China ◽  
Dominant Model ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Aseptic Necrosis ◽  
Increased Risk

<b><i>Background:</i></b> Steroid-induced osteonecrosis of the femoral head (ONFH) is aseptic necrosis of the femoral head caused by glucocorticoid use. Once necrotic femoral head necrosis occurs, it irreversibly affects the quality of life seriously. Studies have shown that the susceptibility to steroid-induced ONFH is likely to be related to the variation of miRNA-coding genes. Therefore, this study aimed was to investigate the effect of <i>MIR3142HG</i> on steroid-induced ONFH. <b><i>Methods:</i></b> Agena MassARRAY was used to genotype <i>MIR3142HG</i> gene rs1582417, rs2431689, rs7727155, and rs17057846 in 199 patients and 725 healthy people. A genetic model and haplotype analysis were used to evaluate the relationship between the <i>MIR3142HG</i> polymorphism and the risk of steroid-induced ONFH. The odds ratio and 95% confidence intervals were obtained through logistic regression to assess the influence of gene polymorphisms on the occurrence of steroid-induced ONFH. <b><i>Results:</i></b> The consequences show that rs7727115 is a protective factor, it could reduce the risk of steroid-induced ONFH, and rs1582417 could increase the risk of steroid-induced ONFH. In the genetic model, rs1582417 was associated with increased risk of alcohol-induced ONFH in dominant model and log-additive model. rs7727115 showed a decreased risk in codominant model, dominant model, and log-additive model. In addition, rs2431689 is related to HDL-C (<i>p</i> = 0.012) and ApoA1 (<i>p</i> = 0.010) levels, and rs17057846 (<i>p</i> = 0.024) is related to ApoB levels. Thelinkage analysis indicated 3 single-nucleotide polymorphisms (rs2431689, rs7727115, and rs17057846) in <i>MIR3142HG</i> with significant chain imbalance. In addition, haplotype “GGG” of <i>MIR3142HG</i> was found out and is harmful for steroid-induced ONFH. <b><i>Conclusion:</i></b> Our results first confirm that the genetic polymorphism of <i>MIR3142HG</i> is associated with steroid-induced ONFH susceptibility in Chinese Han population.

Association of the CD14 C159T and the Toll-like receptor 4 Asp299Gly polymorphisms with various phenotypes of asthma in adults from Crimea

2020 ◽  
Vol 41 (2) ◽  
pp. 134-140
Author(s):  
Yuriy Bisyuk ◽  
Andrew Dubovyi ◽  
Ilona DuBuske ◽  
Viktor Litus ◽  
Lawrence M. DuBuske
Keyword(s):  
Late Onset ◽  
Adult Population ◽  
Additive Models ◽  
Atopic Asthma ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Single Nucleotide ◽  
Gender And Age

Background: This study assessed gene polymorphisms of the CD14 receptor (C-159T) and Toll-like receptor 4 (Asp299Gly) in a patient population in Crimea, Ukraine, stratified by clinical (early versus late onset; frequent versus occasional relapses; fixed versus reversible obstruction) and immunologic (atopic versus nonatopic; eosinophilic; neutrophilic or paucigranulocytic inflammation) subtype. Methods: Two polymorphisms, CD14 C-159T and TLR4 Asp299Gly, were assessed in 331 patients with asthma. The control group included 285 volunteers who were nonatopic. The single nucleotide polymorphisms were studied by using polymerase chain reaction with electrophoretic detection. Results: There were increased odds of asthma development in patients with the Asp299Gly TLR4 mutation compared with the general population underdominant odds ratio (OR) 1.52 [95% confidence interval (CI), 1.00‐2.32] and overdominant (OR 1.55 [95% CI, 1.01‐2.38]) models after adjustment for gender and age. In addition, mutations in this gene decreased the odds of nonatopic asthma in underdominant (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.027), overdominant (OR 0.27 [95% CI, 0.07‐0.96]; p = 0.033), and log-additive models (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.026) compared with the atopic subgroup after adjustment for gender, age, number of exacerbations, and type of airway inflammation. Allele frequencies for CD14 and TLR4 polymorphisms did not show statistical differences between the patients with asthma and the control subjects. Conclusion: CD14 C-159T polymorphisms were not associated with asthma in the adult population in Crimea. TLR4 Asp299Gly polymorphisms were associated with asthma and with decreased odds of nonatopic asthma compared with atopic asthma in the adult population in Crimea.

scholarly journals NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis

2010 ◽  
Vol 70 (4) ◽  
pp. 668-674 ◽  
Author(s):  
P Dieudé ◽  
M Guedj ◽  
J Wipff ◽  
B Ruiz ◽  
G Riemekasten ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Systemic Sclerosis ◽  
Potential Role ◽  
Additive Model ◽  
Nucleotide Polymorphisms ◽  
Fibrosing Alveolitis ◽  
Single Nucleotide ◽  
Risk Alleles ◽  
Caucasian Origin

BackgroundRecent evidence has highlighted a potential role of interleukin 1β (IL-1β) in systemic sclerosis (SSc). NLRP1 provides a scaffold for the assembly of the inflammasome that promotes the processing and maturation of pro-IL-1β. In addition, NLRP1 variants were found to confer susceptibility to autoimmune disorders.ObjectiveTo study a possible association of the NLRP1 rs6502867, rs2670660 and rs8182352, rs12150220 and rs4790797 with SSc in the European Caucasian population.MethodsNLRP1 single nucleotide polymorphisms were genotyped in 3227 individuals comprising a discovery set (870 SSc patients and 962 controls) and a replication set including individuals from Germany (532 SSc patients and 324 controls) and Italy (527 SSc patients and 301 controls), all individuals being of European Caucasian origin.ResultsConditional analyses revealed a significant association for the NLRP1 rs8182352 variant with both anti-topoisomerase-positive and SSc-related fibrosing alveolitis (FA) subsets under an additive model: p=0.0042, OR 1.23 (95% CI 1.07 to 1.41) and p=0.0065 OR 1.19 (95% CI 1.05 to 1.36), respectively. Logistic regression analysis showed an additive effect of IRF5 rs2004640, STAT4 rs7574865 and NLRP1 rs8182352 risk alleles on SSc-related FA.ConclusionsOur results establish NLRP1 as a new genetic susceptibility factor for SSc-related pulmonary fibrosis and anti-topoisomerase-positive SSc phenotypes. This provides new insights into the pathogenesis of SSc, underlining the potential role of innate immunity in particular in the FA-positive SSc subphenotype, which represents a severe subset of the disease.

scholarly journals Associations of Two Obesity-Related Single-Nucleotide Polymorphisms with Adiponectin in Chinese Children

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Lijun Wu ◽  
Liwang Gao ◽  
Xiaoyuan Zhao ◽  
Meixian Zhang ◽  
Jianxin Wu ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Multiple Testing ◽  
Association Studies ◽  
Statistical Significance ◽  
Additive Model ◽  
Recessive Model ◽  
Chinese Children ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Purpose. Genome-wide association studies have found two obesity-related single-nucleotide polymorphisms (SNPs), rs17782313 near the melanocortin-4 receptor (MC4R) gene and rs6265 near the brain-derived neurotrophic factor (BDNF) gene, but the associations of both SNPs with other obesity-related traits are not fully described, especially in children. The aim of the present study is to investigate the associations between the SNPs and adiponectin that has a regulatory role in glucose and lipid metabolism. Methods. We examined the associations of the SNPs with adiponectin in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the study. Results. The SNP rs6265 was significantly associated with adiponectin under an additive model (P=0.02 and 0.024, resp.) after adjustment for age, gender, and BMI or obesity statuses. The SNP rs17782313 was significantly associated with low adiponectin under a recessive model. No statistical significance was found between the two SNPs and low adiponectin after correction for multiple testing. Conclusion. We demonstrate for the first time that the SNP rs17782313 near MC4R and the SNP rs6265 near BDNF are associated with adiponectin in Chinese children. These novel findings provide important evidence that adiponectin possibly mediates MC4R and BDNF involved in obesity.

Histamine H3 receptor gene variants associated with drug abuse in patients with cocaine use disorder

2020 ◽  
Vol 34 (11) ◽  
pp. 1326-1330
Author(s):  
Iñigo Pallardo-Fernández ◽  
José Ramón Muñoz-Rodríguez ◽  
Carmen González-Martín ◽  
Luis F Alguacil
Keyword(s):  
Drug Abuse ◽  
Single Nucleotide Polymorphisms ◽  
Receptor Gene ◽  
Gene Variants ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Histamine H3 Receptor ◽  
Cocaine Use ◽  
H3 Receptor ◽  
Histamine H3

Background: Preclinical work revealed significant interactions between ligands of the histamine H3 receptor and different drugs of abuse. In the case of psychostimulants, the results reported are somewhat controversial and human data are still scarce, despite the fact that an inverse agonist of the H3 receptor (pitolisant) has reached the market after approval for the treatment of narcolepsy. Aims: We have studied associations between histamine H3 receptor gene variants and cocaine use disorder to increase the knowledge of the possible involvement of histamine H3 receptor in drug abuse. Methods: Seven single nucleotide polymorphisms of the histamine H3 receptor gene were genotyped by using a multiplexing assay in 248 samples of subjects with cocaine use disorder and 500 randomized samples of subjects representative of the Spanish population. Results: The study of the epidemiological information associated to the samples revealed that subjects with cocaine use disorder broadly abused alcohol, tobacco and cannabinoids. Two single nucleotide polymorphisms (rs3787430 and rs74627870) were found significantly associated with the occurrence of addiction and one more (rs13042865) was specifically related to the severity of cocaine dependence within drug abusers. Conclusions: The associations found in this study further extend the hypothesis that histamine H3 receptor function could be relevant in drug abuse in general and cocaine addiction in particular.

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