scholarly journals Significant Associations of SOX9 Gene Polymorphism and Gene Expression with the Risk of Osteonecrosis of the Femoral Head in a Han Population in Northern China

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yang Song ◽  
Zhenwu Du ◽  
Ming Ren ◽  
Qiwei Yang ◽  
Yujie Sui ◽  
...  
Keyword(s):  
Gene Expression ◽  
Femoral Head ◽  
Gene Polymorphism ◽  
Protein Expression ◽  
Northern China ◽  
Development Stage ◽  
Control Group ◽  
Cartilage Growth ◽  
Increased Risk ◽  
Sox9 Gene

Sex determining region Y-box 9 (SOX9) is a key transcription factor involved in cartilage formation during the embryonic development stage and cartilage growth and repair after birth. To explore the roles of polymorphism and expression of the SOX9 gene in the development of osteonecrosis of the femoral head (ONFH), we analyzed the polymorphism of rs12601701 [A/G] and rs1042667 [A/C] and the serum protein expression of the SOX9 gene in 182 patients with ONFH and 179 healthy control subjects. Results revealed that the A-A haplotype of SOX9 gene as well as the GG and AA genotypes of rs12601701 was significantly associated with increased ONFH risk (P=0.038) and the risk of bilateral hip lesions of ONFH (P=0.009), respectively. The C-A, A-A, and A-G haplotypes were also statistically associated with the decreased and increased risk of bilateral hip lesions of ONFH (P=0.03,P=0.048, andP=0.013), respectively, while the A-A haplotype closely related to the clinical stages of ONFH (P=0.041). More importantly, the serum SOX9 protein expression of the ONFH group was greatly decreased compared to control group (P=0.0001). Our results first showed that the gene polymorphism and gene expression of SOX9 were significantly associated with the risk and clinical phenotypes of ONFH and also indicate that the SOX9 gene may play a key role in the development of ONFH.

scholarly journals Association of MIR17HG and MIR155HG gene variants with steroid-induced osteonecrosis of the femoral head in the population of northern China

2021 ◽  
Author(s):  
Tingting Liu ◽  
Yuju Cao ◽  
Changxu Han ◽  
Feimeng An ◽  
Tiantian Wang ◽  
...  
Keyword(s):  
Femoral Head ◽  
Gene Mutations ◽  
Density Lipoprotein ◽  
Northern China ◽  
Recessive Model ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Clinical Indicators ◽  
Increased Risk ◽  
The Relationship

Abstract IntroductionSteroid-induced osteonecrosis of the femoral head (ONFH ) is a disease of bone metabolism, and genetic factors are generally considered to play an important role. The purpose of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in MIR17HG and MIR155HG and the risk of steroid-induced ONFH in the population of northern China.MethodsA total of 199 steroid-induced ONFH patients and 506 healthy controls were recruited for the study. Four SNPs of MIR17HG and seven SNPs of MIR155HG were genotyped by Sequenom MassARRAY. ORs and 95% CIs were used to evaluate the relationship between these SNPs and steroid-induced ONFH.ResultsIn the codominant model, patients with the MIR17HG SNPs(rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.79, p = 0.039), in the recessive model, patients with the MIR17HG SNP(rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.78, p = 0.032). Stratified analysis showed that a MIR17HG SNP (rs7318578) and MIR155HG SNPs(rs77218221, rs11911469, rs34904192 and rs4143370) were closely related to different unornamented phenotypes of steroid-induced ONFH. Analysis of the clinical indicators revealed significant differences in high-density lipoprotein (HDL-C) levels between the ONFH group and the control group (p = 0.005). MIR17HG SNP(rs75267932) and MIR155HG SNPs(rs77699734, rs1893650 and rs34904192) were correlated with different lipid indexes.ConclusionOur results confirm that MIR17HG and MIR155HG gene mutations are associated with steroid-induced ONFH susceptibility in the population of northern China, providing new evidence for the early detection and prevention of ONFH.

Associations of IGFBP3 Gene Polymorphism and Gene Expression with the Risk of Osteonecrosis of the Femoral Head in a Han Population in Northern China

2016 ◽  
Vol 35 (12) ◽  
pp. 836-844 ◽  
Author(s):  
Yang Song ◽  
Zhenwu Du ◽  
Qiwei Yang ◽  
Ming Ren ◽  
Yujie Sui ◽  
...  
Keyword(s):  
Gene Expression ◽  
Femoral Head ◽  
Gene Polymorphism ◽  
Northern China ◽  
Han Population

scholarly journals Association of MIR17HG and MIR155HG gene variants with steroid-induced osteonecrosis of the femoral head in the population of northern China

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Tingting Liu ◽  
Yuju Cao ◽  
Changxu Han ◽  
Feimeng An ◽  
Tiantian Wang ◽  
...  
Keyword(s):  
Femoral Head ◽  
High Density Lipoprotein ◽  
Gene Mutations ◽  
Density Lipoprotein ◽  
Northern China ◽  
High Density ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
The Relationship

Abstract Introduction Steroid-induced osteonecrosis of the femoral head (ONFH) is a disease of the bone. Metabolism and genetic factors are generally considered to play an important role. The purpose of this study was to investigate the relationship between single-nucleotide polymorphisms (SNPs) in MIR17HG and MIR155HG and the risk of steroid-induced ONFH in the population of northern China. Methods A total of 199 steroid-induced ONFH patients and 506 healthy controls were recruited for the study. Four SNPs of MIR17HG and seven SNPs of MIR155HG were genotyped by Sequenom MassARRAY. ORs and 95% CIs were used to evaluate the relationship between these SNPs and steroid-induced ONFH. Results In the codominant model, patients with the MIR17HG SNPs (rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.79, p = 0.039); in the recessive model, patients with the MIR17HG SNP (rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.78, p = 0.032). Stratified analysis showed that a MIR17HG SNP (rs7318578) and the MIR155HG SNPs (rs77218221, rs11911469, rs34904192 and rs4143370) were closely related to different unornamented phenotypes of steroid-induced ONFH. Analysis of the clinical indicators revealed significant differences in high-density lipoprotein (HDL-C) levels between the ONFH group and the control group (p = 0.005). In the MIR17HG SNP (rs75267932), patients with different genotypes had different levels of triglyceride (TG). The MIR155HG SNPs (rs77699734, rs1893650, and rs34904192) showed differences in triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels in patients with different genotypes. Conclusion Our results confirm that MIR17HG and MIR155HG gene mutations are associated with steroid-induced ONFH susceptibility in the population of northern China, providing new evidence for the early detection and prevention of ONFH.

Gene Polymorphisms of Costimulatory Molecules: CTLA-4/CD28/ICOS Are Associated with B-Cell Chronic Lymphocytic Leukemia (B-CLL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2074-2074 ◽  
Author(s):  
Irena Frydecka ◽  
Katarzyna Suwalska ◽  
Edyta Pawlak ◽  
Lidia Karabon ◽  
Anna Tomkiewicz ◽  
...  
Keyword(s):  
T Cell ◽  
Gene Polymorphism ◽  
Costimulatory Molecules ◽  
N Gene ◽  
Control Group ◽  
Stepwise Logistic Regression ◽  
Polymorphism Analysis ◽  
Cell Functions ◽  
Increased Risk ◽  
Risk Of Cancer

Abstract There are strong evidences that altered immunological function entails an increased risk of cancer. Cytotoxic T-lymphocyte antigen 4 (CTLA-4), CD28, and Inducible co-stimulator (ICOS) are costimulatory molecules provide regulatory signals for T-cell activation. CD28 and ICOS potently enhance T-cell functions, while activation of T-cells is subsequently downregulated by CTLA-4. The abnormal expression of costimulatory molecules may be caused by polymorphisms of genes encoding these molecules. The extended study was undertaken to evaluate the association between the polymorphisms: CTLA-4+49A/G, CTLA-4-319C/T, CTLA-4(AT)n, CD28+17C/T, ICOS(GT)n and susceptibility to B-CLL in a Polish population. All together 124 B-CLL patients and 202 controls were studied. Single nucleotide polymorphisms were typed by minisequencing. The microsatellite polymorphisms were studied by PCR and fuorescence based technique. The distribution of -319T/C alleles and genotypes differed significantly between groups. The frequency of T allele and T phenotype was increased in patients with respect to controls (p=0.01, OR=1.74, 1.13∼95%CI∼2.68; p=0.01, OR =1.85, 1.13∼95%CI∼3.04, respectively). CTLA-4+49A/G and CTLA-4 (AT)n did not correlate with B-CLL. The analysis of the CD28+17C/T showed that the presence of C allele and C phenotype increased the OR of B-CLL by 1.97 and 2.07, respectively (p=0.002, 1.28∼95%CI ∼3.03; p=0.003, 1.27∼95%CI ∼3.38). For ICOS(GT)n gene polymorphism analysis we combined the alleles into 3 groups: (s)- short-alleles with 8 and 9 repeats, (m) -middle- with 10 and 11 and (l)- long- 12 and more repeats. The global distribution of alleles and genotypes was significantly different in patients and controls (p=0.00008 and p=0.00006, respectively). Individuals possessing (s) alleles were 2.75 times more prone to B-CLL than others (p=0.0000, OR=2.75, 1.67∼95%CI∼4.55), while carrying (l) alleles were protected to B-CLL (p=0.004, OR=0.47, 0.29∼95%CI∼0.79). The genotype (s)/(m) was overrepresented in patients (p=0.004, OR=2.29, 1.28∼95%CI∼2.09), but (l)/(l) individuals appeared more frequently in controls (p=0.002, OR=0.07, 0.00 ∼95%CI∼0.44). The haplotype association study of three polymorphic sites: CTLA-4-319C/T and CD28+17C/T and ICOS (s)/(m)/(l), which correlated with B-PBL in univariante analysis, showed that the distribution of haplotypes was different in cases and control, global p value was p= 3 ×108. Remarkable, the haplotypes T/C/(s) and T/T/(s) were presented only in B-CLL (p=0.0004, OR=62072, 3540∼95%CI∼1088238; p=0.00003, OR=3447, 203∼95%CI∼58334, respectively) while the haplotype C/T/(l) was significantly more frequent in control group as compared to B-CLL (p=0.000003, OR=0.3, 0.18∼95%CI∼0.51). B-CLL patients and controls polymorphic features for CTLA-4-319C/T, CD28IVS3+17C/T, ICOS (GT)n were subjected to multivariate forward stepwise logistic regression analysis. It appeared that C phenotype at CD28 T17int3C site increased twice risk of B-CLL (p=0.004, OR=2.09; 1.26∼95%CI∼3.48), while genotype (m)/(l) or (l)/(l) for ICOS gene protected from disease (p=0,0009, OR=0,41; 0,24∼95%CI∼0,69). We reported for the first time that the gene polymorphism of costimulatory molecules: CTLA-4/CD28/ICOS contribute to susceptibility to B-CLL.

scholarly journals PECAM-1 gene polymorphism (rs668) and subclinical markers of carotid atherosclerosis in patients with type 2 diabetes mellitus

2016 ◽  
Vol 19 (1) ◽  
pp. 63-70 ◽  
Author(s):  
D Popović ◽  
J Nikolajević Starčević ◽  
M Šantl Letonja ◽  
J Makuc ◽  
A Cokan Vujkovac ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Gene Polymorphism ◽  
Carotid Atherosclerosis ◽  
Control Group ◽  
Minor Effect ◽  
Initial Examination ◽  
Increased Risk

ABSTRACTThe platelet endothelial cell adhesion molecule 1 (PECAM-1) plays an important role in many inflammatory processes, including the development of atherosclerosis. Polymorphism rs668 of the PECAM-1 gene (373C/G) is functional, and it was reported to be associated with increased serum levels of PECAM-1. We investigated the association between the rs668 polymorphism of PECAM-1 and subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). Five hundred and ninety-five T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Geno-typing of the PECAM-1 gene polymorphism (rs668) was performed using KASPar assays. The control examinations were performed 3.8 ± 0.5 years after the initial examination. Higher CIMT was found in patients with T2DM in comparison with subjects without T2DM. Statistically sig-nificantly faster progression of the atherosclerotic markers was shown in subjects with T2DM in comparison with the control group. When adjusted to other risk factors, the rs668 GG genotype was associated with an increased risk of carotid plaques in subjects with T2DM. We concluded that our study demonstrated a minor effect of the rs668 PECAM-1 on markers of carotid atherosclerosis in subjects with T2DM.

scholarly journals Association of αENaC p. Ala663Thr Gene Polymorphism With Sudden Sensorineural Hearing Loss

2021 ◽  
Vol 12 ◽  
Author(s):  
Jialei Chen ◽  
Jing He ◽  
Jing Luo ◽  
Shixun Zhong
Keyword(s):  
Hearing Loss ◽  
Gene Polymorphism ◽  
Sensorineural Hearing Loss ◽  
Allele Frequency ◽  
Low Frequency ◽  
Sudden Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Control Group ◽  
Increased Risk ◽  
Significant Difference

Objective: The etiology of sudden sensorineural hearing loss (SSNHL) is still unknown. It has been demonstrated that normal endolymph metabolism is essential for inner ear function and that epithelial sodium channels (ENaC) may play an important role in the regulation of endolymphatic Na+. This study aimed to explore the potential association between αENaC p. Ala663Thr gene polymorphism and SSNHL.Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine the genotype and allele frequency of the αENaC p. Ala663Thr polymorphism in 20 cases of low-frequency SSNHL (LF-SSNHL), 19 cases of high-frequency SSNHL (HF-SSNHL), 31 cases of all frequency SSNHL (AF-SSNHL), 42 cases of profound deafness SSNHL (PD-SSNHL), and 115 normal controls.Results: The T663 allele was found to be significantly associated with an increased risk of LF-SSNHL (p = 0.046, OR = 2.16, 95% CI = 1.01–4.62). The TT genotype and T663 allele, on the other hand, conferred a protective effect for PD-SSNHL (AA vs. TT: p = 0.012, OR = 0.25, 95% CI = 0.08–0.74; A vs. T: p = 0.001, OR = 0.36, 95% CI = 0.21–0.61). However, there was no statistically significant difference in genotype or allele frequency between the two groups (HF-SSNHL and AF-SSNHL) and the control group.Conclusion: The αENaC p. Ala663Thr gene polymorphism plays different roles in different types of SSNHL.

NCF4 gene polymorphism, level of glutathione and glycated hemoglobin in type 2 diabetics with coronary artery disease

2021 ◽  
pp. 37-47
Author(s):  
Ю.Э. Азарова
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Gene Polymorphism ◽  
Glycated Hemoglobin ◽  
Control Group ◽  
Maldi Tof ◽  
Genotype Frequencies ◽  
Increased Risk ◽  
Artery Disease

Общим патогенетическим звеном сахарного диабета 2 типа (СД2) и ишемической болезни сердца (ИБС) является окислительный стресс, развивающийся в результате дисбаланса продукции активных форм кислорода (АФК) и их обезвреживания системой антиоксидантной защиты. Нейтрофильный цитозольный фактор 4 (NCF4) непосредственно вовлечен в синтез супероксид-аниона в составе НАДФН-оксидазы. Целью настоящего исследования стало изучение ассоциаций восьми однонуклеотидных полиморфизмов гена NCF4 rs5995355 (A>G), rs5995357 (T>A), rs1883112 (G>A), rs4821544 (G>A), rs760519 (T>C), rs729749 (C>T), rs2075938 (G>A) и rs2075939 (C>T) с предрасположенностью к СД2, а также с риском развития ИБС у пациентов с СД2. В исследование включено 1579 пациентов с СД2 (у 448 из которых была также диагностирована ИБС) и 1627 условно здоровых добровольцев. Генотипирование выполнено методом MALDI-TOF масс-спектрометрии на платформе MassArray Analyzer 4. Статистическую обработку полученных данных проводили с помощью онлайн программы SNPStats. Частоты аллелей и генотипов изучаемых SNPs у больных СД2 не отличались от таковых в группе контроля (р>0,05). Установлены ассоциации генотипов rs4821544-C/С (OR 1,71, 95CI 1,12-2,59, р=0,013) и rs5995357-А/А (OR 3,74, 95CI 1,14-12,31, р=0,026) с предрасположенностью к ИБС у больных СД2 женщин. Несмотря на отсутствие ассоциаций изучаемых SNPs гена NCF4 с ИБС у мужчин, именно у представителей мужского пола выявлены ассоциации гаплотипической структуры NCF4 (р=0,0064), а также гаплотипов Н2 (OR 1,79, 95CI 1,16-2,76, р=0,0085) и Н3 (OR 1,77, 95CI 1,06-2,97, р=0,03) с повышенным риском развития ИБС при СД2. Кроме того, выявлены не зависящие от пола ассоциации генотипа rs4821544-С/С с повышенным уровнем гликированного гемоглобина HbA1c (р=0,032) и окисленного глутатиона плазмы крови (p=0.049) у пациентов с ИБС и СД2. В этой же категории больных носительство гаплотипов Н4 rs5995355G-rs5995357A-rs1883112G-rs4821544C-rs760519T-rs729749C-rs2075938G-rs2075939C и Н10 rs5995355A-rs5995357T-rs1883112G-rs4821544C-rs760519T-rs729749C-rs2075938A-rs2075939C гена NCF4 ассоциировалось с повышением содержания HbA1c на 8,67% (р=0,011) и 6,27% (р=0,038), соответственно. Полученные данные свидетельствуют о значимом вкладе полиморфизма гена NCF4 в патогенез ИБС у пациентов с СД2 и создают научный задел для разработки таргетной терапии и профилактики этой патологии. A common pathogenic link in type 2 diabetes mellitus (T2D) and coronary artery disease (CAD) is oxidative stress, which develops as a result of an imbalance in the production of reactive oxygen species (ROS) and their neutralization by the antioxidant defense system. Neutrophilic cytosolic factor 4 (NCF4) is directly involved in the synthesis of superoxide anion as part of NADPH oxidase. In this regard, the purpose of this study was to investigate the associations of eight single nucleotide polymorphisms of the NCF4 gene rs5995355 (A>G), rs5995357 (T>A), rs1883112 (G>A), rs4821544 (G>A), rs760519 (T>C), rs729749 (C>T), rs2075938 (G>A), rs2075939 (C>T) with a predisposition to T2D, as well as the risk of developing CAD in patients with T2D. The study included 1579 patients with T2D (448 of them were also diagnosed with CAD) and 1627 relatively healthy volunteers. Genotyping was performed using MALDI-TOF mass spectrometry on the MassArray Analyzer 4 platform. Statistical processing of the obtained data was carried out using the SNPStats online program. The allele and genotype frequencies of the studied SNPs in T2D patients did not differ from those in the control group (p>0.05). Associations of genotypes rs4821544-C/C (OR 1.71, 95CI 1.12-2.59, p=0.013) and rs5995357-A/A (OR 3.74, 95CI 1.14-12.31, p=0.026) with a predisposition to CAD in diabetic females were established. Despite the absence of associations of the studied SNPs NCF4 with CAD in males, associations of the haplotype structure of NCF4 (p=0.0064), as well as the haplotypes H2 (OR 1.79, 95CI 1.16-2.76, p=0.0085) and H3 (OR 1.77, 95CI 1.06-2.97, p=0.03) with an increased risk of CAD were observed exclusively in diabetic males. In addition, a sex-independent relationship of the rs4821544-C/C genotype with an increased level of glycated hemoglobin (p=0.032) and oxidized glutathione (p=0.049) was revealed in patients with CAD and T2D. In the same category of patients haplotypes H4 rs5995355G-rs5995357A-rs1883112G-rs4821544C-rs760519T-rs729749C-rs2075938G-rs2075939C and H10 rs5995355A-rs5995357T-rs1883112G-rs4821544C-rs760519T-rs729749C-rs2075938A-rs2075939C of NCF4 gene were associated with an increase in the content of HbA1c 8.67 % (p=0.011) and 6.27% (p=0.038), respectively. The data obtained indicate a significant contribution of the NCF4 gene polymorphism to the pathogenesis of CAD in patients with T2D and create a scientific basis for the development of targeted therapy and prevention of this pathology.

Research on the Mechanism of Asiaticoside Inhibiting Osteoclast Differentiation and Promoting the Recovery of Steroid-Induced Osteonecrosis of the Femoral Head (SIONFH)

2021 ◽  
Vol 11 (8) ◽  
pp. 1606-1611
Author(s):  
Meijing Miao ◽  
Liping Guo ◽  
Pengfei Su ◽  
Jinshan Ji ◽  
Baoli Li
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Bone Marrow ◽  
Femoral Head ◽  
Protein Expression ◽  
Western Blot ◽  
Osteoclast Differentiation ◽  
Culture Fluid ◽  
Qrt Pcr

Our study aims to assess whether asiaticoside promotes the recovery of SINOFH by inhibiting bone marrow stem cells (BMSCs) differentiation into osteoclasts (OC). BMMs were induced to form OC system by dexamethasone in vitro and ELISA detected the expression of OC-related genes formation by asiaticoside. BMSCs were cultured followed by analysis of BMSCs morphology under microscope, gene expression by qRT-PCR. TRACP and c-Src level by western blot, RANKL, OPG and TRACP5b level by ELISA. Asiaticoside inhibited the expression of OC formation in SIONFH. The expression of OC-related genes increased with the induction days. With the increasing of induction days, asiaticoside level in culture fluid was decreased. While after asiaticoside interference, OCrelated genes and proteins levels were significantly down-regulated. Aasiaticoside can significantly increase the RANKL signaling protein expression. In conclusion, asiaticoside promotes the recovery of SINOFH by inhibiting BMSCs differentiation into OC.

scholarly journals Association of Interleukin-6 Gene Promoter Polymorphism with Coronary Artery Disease in Pakistani Families

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Humayoon Shafiq Satti ◽  
Sabir Hussain ◽  
Qamar Javed
Keyword(s):  
Gene Expression ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Gene Polymorphism ◽  
Interleukin 6 ◽  
Promoter Polymorphism ◽  
Binary Logistic Regression Model ◽  
Increased Risk ◽  
Hs Crp ◽  
Artery Disease

Interleukin-6 (IL-6) is a well-known inflammatory cytokine and suggested to be involved in the development of coronary artery disease (CAD). IL-6 gene expression has been investigated with controversy in CAD patients. This study investigates the association of the IL-6 gene expression with CAD, the molecular basis for the regulation of interleukin-6 expression in a Pakistani population. Our data show that the serum IL-6 levels were increased in patients with CAD compared with healthy controls and that the IL-6 gene polymorphism at -174 was more prevalent in CAD cases. There was a statistically significant association between the IL-6 gene polymorphism and CAD, which may be associated with an increased risk for the disease. Moreover, circulating IL-6 and hs-CRP levels were significantly higher in patients with CC genotype (P<0.0001andP<0.0001, resp.). In a binary logistic-regression model, an independent association was found between CAD and increased serum IL-6 and hs-CRP levels and -174G>C polymorphism. This is the first report on the IL-6 expression and the IL-6 gene polymorphism in patients with CAD from Pakistan, and hence it highlights a novel risk factor for the disease.

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