Osteoprotegerin Gene Polymorphisms Research Articles

Analysis of angiotensin II type 1 receptor and osteoprotegerin gene polymorphism on the risk of cardiovascular mortality risk and progressivity of chronic kidney disease.

Chronic kidney disease (CKD) is a significant global public health issue with increased risk of atherosclerotic cardiovascular disease (ASCVD) and cardiovascular mortality. Single nucleotide polymorphisms (SNPs) on angiotensin II type 1 receptor (AT1R) A1166C and osteoprotegerin (OPG) C950T gene have received significant attention as a genetic risk factor for cardiovascular disease and CKD. This was a cross-sectional study involving 75 adults with CKD recruited from Nephrology Outpatient Clinics of Universitas Airlangga Hospital, Surabaya, Indonesia. Demographic data was obtained from interviews and medical records. The "CKD Patch" application was used to asses ASCVD and cardiovascular mortality risk scores. Statistical analysis was performed by using SPSS version 26. We detected four different AT1R gene polymorphisms (A1166C, A1160C, G1170T, and G1181C) and two OPG gene polymorphisms (T950C and G1181C) in Indonesian CKD patients. A1160C and G1181C polymorphisms were novel SNPs, newly discovered in this research. No significant association was found between AT1R SNPs and kidney prognostic markers or ASCVD risk/mortality risk scores. However, for OPG C950T we found that TT genotype had a significantly higher ACR than TC or CC genotype (P=0.032). As for OPG G1181C, we found that GG genotype had a higher serum creatinine and albumin to creatinine ratio compared to GC and CC genotypes (P=0.004 and 0.029, respectively). Genotype GC for OPG G1181C was also shown to be protective for having better kidney markers and lowest cardiovascular mortality risk compared to GG and CC genotypes (P=0.018 and 0.032, respectively). Increased ASCVD risk and mortality risk score was not found on individuals with AT1R gene SNPs. However, for OPG gene polymorphism, C950T and G1181C were associated with kidney progression and cardiovascular mortality.

Osteoprotegerin gene polymorphisms in postmenopausal women with knee osteoarthritis

Aim – to investigate the associations of rs3134069, rs4355801 and rs3102735 polymorphisms in the TNFRSF11B gene with knee osteoarthritis in postmenopausal women.
 Material and methods. 483 postmenopausal women were examined, including 157 patients with knee osteoarthritis. The remaining 326 women had no signs of joint disease and formed the control group. All examined women were tested using real-time polymerase chain reaction for single nucleotide polymorphisms rs3134069, rs4355801 and rs3102735 in the TNFRSF11B gene.
 Results. It was found that genotypes distribution of polymorphisms rs3134069, rs4355801 and rs3102735 in the TNFRSF11B gene in the total group of examined women (n=483) corresponded to the Hardy-Weinberg law (p0,05). Analysis of the polymorphic variants frequency in the TNFRSF11B gene revealed an increased frequency of AC or CC genotypes of rs3134069 polymorphism in patients with knee osteoarthritis (OR=1,91; 95% CI: 1,10–3,32; p=0,030). Also, among patients with osteoarthritis, the allele C registration frequency of the above polymorphism was increased (OR=1,78; 95% CI: 1,06–2,99; p=0,040). For two other studied polymorphisms in the TNFRSF11B gene (rs4355801 and rs3102735) no association with knee osteoarthritis was found (p0,05).
 Conclusion. The increased frequency of genotypes AC or CC registration, as well as allele C of rs3134069 polymorphism in the TNFRSF11B gene in postmenopausal women with knee osteoarthritis indicates the important role of TNFRSF11B gene mutations in the osteoarthritis development and progression. Further research in this direction is of great interest both for a deeper understanding of the disease pathogenesis and for the development of personalized approach criteria in the prevention and treatment of knee osteoarthritis in postmenopausal women.

Association of rs2073618 polymorphism and osteoprotegerin levels with hypertension and cardiovascular risks in patients with type 2 diabetes mellitus

There are reports of link of osteoprotegerin (OPG) gene polymorphism to type-2 diabetes (T2D) and hypertension (HTN). The objective of the study was to assess the allele frequency of OPG (rs2073618) gene polymorphism and its association with heart rate variability (HRV) and blood pressure variability profile as CVD risks in diabetes mellitus patients with hypertension undergoing treatment. T2D patients on treatment without hypertension (n = 172), with hypertension (n = 177) and 191 healthy volunteers were recruited for the study. Their blood pressure variability including baroreflex sensitivity (BRS), heart rate variability (HRV), OPG, insulin, lipid profile, receptor-activator for NFkB (RANK), receptor-activator for NFkB-Ligand (RANKL), and tumor necrosis factor-α (TNF-α) were estimated. Allele frequency of OPG (rs2073618) gene polymorphism was assessed from the DNA samples. BRS and HRV indices were decreased, and RANKL/OPG and TNF-α were increased in T2D and T2D + HTN groups, respectively compared to healthy control group. The reduction in BRS was contributed by increased inflammation and reduced SDNN of HRV in GG genotype in T2D + HTN. In GG + GC subgroup, it was additionally contributed by rise in RANKL/OPG level (β − 0.219; p 0.008). Presence of mutant GG genotype contributed to the risk of hypertension among T2D patients (OR 3.004) as well as in general population (OR 2.79). It was concluded that CV risks are more in T2D patients with HTN expressing OPG rs2073618 gene polymorphism.

Bone mineral density in egyptian children with juvenile idiopathic arthritis: possible correlation to serum RANKL / osteoprotegerin (OPG) ratio and OPG gene polymorphisms

BackgroundChildren with juvenile idiopathic arthritis (JIA) are at higher risk of decreased bone mineral density (BMD) compared with healthy children due to genetic, disease and medication-related causes. This study aims to investigate the possible effects of osteoprotegerin (OPG) gene polymorphisms and serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor κB-ligand (RANKL) and RANKL/OPG ratio on BMD in children with JIA.MethodsOPG gene rs2073617, rs3134069, serum RANKL, OPG and RANKL/OPG ratio were evaluated in 60 JIA children and 100 matched healthy controls. BMD was evaluated by lumbar dual energy X-ray absorptiometry (DEXA) according to which patients were classified in 2 groups (DEXA z-score above and below − 2). Composite disease activity was measured using the Juvenile Arthritis Disease Activity Score (JADAS) 27-joints. Articular damage was scored using the juvenile arthritis damage index (JADI).ResultsPatients aged 12.05 ± 3.2 years, included 38 females and 31% had BMD z-score below-2. Systemic-onset JIA was the most frequent phenotype (38%). Genotypes and alleles frequencies of the 2 studied polymorphisms did not differ between patients and controls (p > 0.05 for all) while serum RANKL and RANKL/OPG ratio were significantly higher in patients compared to controls (p = < 0.001 and 0.03 respectively). Patients with BMD < -2 had significantly greater frequencies of rs2073617 TT genotype and T allele (p < 0.001), higher serum RANKL, RANKL/OPG ratio (p = 0.01, 0.002), female predominance (p = 0.02), higher articular and extra-articular damage index (p = 0.008,0.009) and more frequent steroid usage (p = 0.02) compared to patients with BMD z-score >-2. Multivariate analysis showed rs2073617 TT genotype, RANKL/OPG ratio, long disease duration (above 36 months) and use of steroid to be associated with decreased BMD (p = 0.03,0.04,0.01,0.01 respectively) in JIA children.ConclusionsEgyptian children with JIA have decreased BMD. rs2073617 TT genotype and T allele, RANKL/OPG ratio are possible determinants of reduced BMD in JIA. Our results underline the importance of frequent monitoring of BMD in JIA children and trying to control disease activity to preserve long term bone health.

Association of OPG and RANKL gene polymorphisms with bone mineral density in Indian women

Osteoprotegerin (OPG) and receptor activator of the NF-kB ligand (RANKL) are key players in bone remodelling. Reports show that OPG and RANKL gene polymorphisms are associated with osteoporosis and fracture risk. The aim of this study was to examine the influence of 5 single nucleotide polymorphisms (SNPs) in OPG and RANKL gene on bone mineral density (BMD) in Indian women. The study included 374 healthy Indian women. Kompetitive Allele Specific PCR (KASP) was used for genotyping. There was a significant difference in the BMD at spine between genotypes of OPG rs2073618 (CC: 0.988 ± 0.167 CG: 1.023 ± 0.17 GG: 1.053 ± 0.155; p = 0.039) which was lost upon adjustment for age and BMI (p = 0.087). Multiple linear regression revealed that genotypes of OPG rs2073618 (β = 0.098; p = 0.027) and rs3102735 (β = 0.092; p = 0.038) are predictors of BMD at spine in Indian women. We did not observe any association of SNPs in RANKL gene with BMD. Thus, SNPs rs2073618 and rs3102735 in OPG gene may influence BMD at spine in Indian women.

Osteoprotegerin Gene Polymorphisms Are Associated with Subclinical Atherosclerosis in the Mexican Mestizo Population.

Subclinical atherosclerosis (SA) is the presence of coronary calcification in the absence of cardiovascular symptoms, and it usually progresses to atherosclerotic disease. Studies have shown an association of osteoprotegerin gene (OPG) variants with calcification process in cardiovascular diseases; however, to this day there are no studies that evaluate individuals in the asymptomatic stage of atherosclerotic disease. Therefore, the purpose of this study was to analyze the association of four genetic variants and haplotypes of the OPG gene with the development of SA, through TaqMan genotyping assays. We also aimed to identify potential response elements for transcription factors in these genetic variants. The study included 1413 asymptomatic participants (1041 were controls and 372 were individuals with SA). The rs3102735 polymorphism appeared as a protective marker (OR = 0.693; 95% CI = 0.493–0.974; pheterozygote = 0.035; OR = 0.699; 95% CI = 0.496–0.985; pcodominant 1 = 0.040) and two haplotypes were associated with SA, one as a decreased risk: GACC (OR = 0.641, 95% CI = 0.414–0.990, p = 0.045) and another as an increased risk: GACT (OR = 1.208, 95% CI = 1.020–1.431, p = 0.029). Our data suggest a lower risk of SA in rs3102735 C carriers in a representative sample of Mexican mestizo population.

Predictors of decreased bone mineral density in childhood systemic lupus erythematosus: possible role of osteoprotegerin gene polymorphisms.

This study aims to explore effects of osteoprotegerin (OPG) gene polymorphisms and other possible factors on bone mineral density (BMD) in children with systemic lupus erythematosus (SLE). Osteoprotegerin gene rs2073617 and rs3134069 were evaluated in 74 SLE patients and 100 controls then genotypes, alleles and haplotypes' frequencies were compared between cases and controls and between patients with BMD z-scores above and below -2 evaluated by dual energy X-ray absorptiometry (DEXA). Disease activity was evaluated by SLE disease activity index (SLEDAI). The patients aged 14.01±2.6 years and included 57 (77%) females and 27 (36%) patients with BMD z-score below -2. Genotypes, alleles, and haplotypes frequencies did not differ between patients and controls (p>0.05 for all). Rs3134069 GG genotype and G allele (p=0.001, 0.002) and rs2073617 TT genotype and T allele (p=0.01, 0.006) were significantly higher in patients with BMD below -2. Cumulative glucocorticoids dose, disease duration, and SLEDAI scores were higher in patients with BMD below -2 (p=0.01, 0.01, <0.001, respectively). Regression analysis showed T allele of rs2073617, duration of illness (above 36 months), and cumulative SLEDAI (above 10) as independent predictors of decreased BMD (p 0.02, 0.003, and 0.002, respectively). This is the first study to demonstrate OPG gene influence on BMD in children with SLE. The studied SNPs are not risk for developing SLE but, rs2073617T allele is a possible predictor for reduced BMD in SLE. Other predictors include long disease duration and high activity supporting that osteoporosis in SLE is multifactorial.

A New Biomarker on Bone Resorption in Chronic Otitis Media: Osteoprotegerin and NLRP3 Inflammasome Gene Polymorphisms.

Chronic Otitis Media (COM) is a chronic inflammation of the middle ear and mastoid with persistent membrane perforation and hearing loss. Osteoprotegerin (OPG) and NOD like receptor protein 3 (NLRP3) play an important role in bone metabolism. The aim of the study was to investigate the role of OPG and NLRP3 gene polymorphism on ossicular chain resorption in COM. Fourty COM patients and 20 healhty control group were included in the study. While 20 patients underwent ossiculoplasty, 20 patients underwent type 1 tympanoplasty. DNA was isolated from peripheral blood using the DNA kit. OPG gene c.226A > C (p.Thr76Pro) and NLRP3 gene c.592G > A (p. Val198Met) polymorphisms were genotyped using melting curve analysis technique. NLRP3 gene polymorphism were determined in 6 of 20 patients (30%) in ossiculoplasty group, 4 of 20 patients (20%) in type 1 tympanoplasty group and 3 of 20 patients (15%) in control group. OPG gene polymorphism were determined in 5 of 20 patients (25%) in ossiculoplasty group, 3 of 20 patients (15%) in type 1 tympanoplasty group and 1 of 20 patients (5%) in control group, respectively. There was no statistically significant difference between groups regarding to results. Although the difference was not significant NLRP3 and OPG gene polymorphisms were higher in the ossiculoplasty group. Since NLRP3 and OPG gene polymorphisms were determined to be higher numerically in the ossiculoplasty group, OPG and NLRP3 gene regulation system may have an effect on ossicular chain destruction in COM.

The association of OPG polymorphisms with risk of osteoporotic fractures: A systematic review and meta-analysis.

Background:Subjects with low bone mineral density and osteoporosis are more likely to suffer osteoporotic fractures during their lifetime. Polymorphisms in osteoprotegerin (OPG) gene are found to be associated with low bone mineral density and osteoporosis risk but their association with fracture risk is inconclusive. Here, we performed a meta-analysis to investigate the relationship between OPG polymorphisms with susceptibility to osteoporotic fractures.Methods:Eligible studies investigating the association between common OPG polymorphisms (A164G, T245G, T950C, and G1181C) and risk of osteoporotic fracture were retrieved from PubMed, EMBASE, Web of Science, and the Cochrane Library. Odds ratio (OR) and the 95% confidence interval (CI) were calculated in the allelic, dominant, recessive, and homozygous model. Subgroup analyses of vertebral fractures, Caucasians, and postmenopausal women were also performed.Results:A total of 14 studies comprising 5459 fracture cases and 9860 non-fracture controls were included. A163G was associated with fracture risk in dominant (OR = 1.29, 95%CI 1.11–1.50), recessive (OR = 1.64, 95%CI 1.10–2.44), and homozygous model (OR = 1.73, 95%CI 1.16–2.59). T245G was significantly correlated with susceptibility to fractures in all genetic models. Subjects with CC genotype of T950C had a reduced risk of fracture compared to those with CT or TT genotypes (OR = 0.81, 95%CI 0.70–0.94, P = .004). Subgroup analysis showed that A163G and T245G but not T950C and G1181C were associated with vertebral fracture risk.Conclusion:OPG A163G and T245G polymorphisms were risk factors of osteoporotic fractures while T950C had a protective role. These polymorphisms can be used as predictive markers of fractures.

Association of serum osteoprotegerin and osteoprotegerin gene polymorphism with subclinical carotid artery atherosclerosis and disease activity in rheumatoid arthritis patients

Aim of the workTo investigate the association of single nucleotide polymorphism (SNP) (rs2073618) of the OPG gene and of serum OPG with subclinical carotid atherosclerosis in RA patients. Patients and methodsEighty RA patients with no previous history of a cardiovascular disease were studied and forty healthy controls were enrolled in the study. Carotid atherosclerosis was evaluated by high-resolution B-mode ultrasound and the carotid intimal medial thickness (CIMT) measured. rs2073618 OPG genotyping was performed by polymerized chain reaction (PCR) and serum OPG concentrations were measured. The high sensitive C reactive protein (hs-CRP), rheumatoid factor (RF) titer and anti-cyclic citrullinated peptide (anti-CCP) were assessed. The disease activity score (DAS28) was evaluated. ResultsThe patients mean age was54.1 ± 6.2 years, disease duration of 12.5 ± 8.5 years and were 72 females and 8 males. Increased IMT was found in 38 patients, 40 age and sex matched controls were included. Patients with atherosclerosis (n = 38) had longer disease duration, higherDAS28, hs-CRP, RF titer and anti-CCP. The serum OPG levels were higher in patients with atherosclerosis (1106.4 ± 1157.1 ng/l) compared to those without (658.3 ± 151.1 ng/l)(p = 0.001). Serum OPG significantly correlated with disease duration (r = 0.42, p = 0.005), DAS28 (r = 0.53, p = 0.001), hs-CRP (r = 0.41, p = 0.007), anti-CCP (r = 0.47, p = 0.003) and mean CIMT (r = 0.37, p = 0.02). The frequencies of CC, CG and GG genotypes were comparable between those with and without atherosclerosis (39.5%, 50%, 10.4% vs 42.9%, 47.6% and 9.5% respectively). Conclusionrs2073618 OPG gene may not be associated with subclinical atherosclerosis, although the serum level could be a reliable marker for disease activity and for early detection of carotid artery atherosclerosis in RA.

Effect of Osteoprotegerin and XRCC3 Genes Polymorphisms with the Occurrence of Left Ventricular Hypertrophy in Hypertensive Patients

Background: High blood pressure is associated with adverse morphological and functional changes in the cardiovascular system, including left ventricular hypertrophy (LVH). Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily of cytokines. X-ray repair cross-complementing protein 3 (XRCC3) is involved in the repair pathway for double-strand breaks (DSBs). We assessed the association of osteoprotegerin and XRCC3 gene polymorphisms with the occurrence of left ventricular hypertrophy in hypertensive patients. Patients and methods: The study included 50 hypertensive patients: 25 with LVH (group A) and 25 without LVH (group B). All cases were subjected to complete history taking and clinical examination. ECG and echocardiography were done. LV mass was calculated to detect the presence or absence of LV hypertrophy. DNA was extracted from blood samples, and then, each DNA sample was amplified in PCRs, to detect osteoprotogrin and XRCC3 gene polymorphisms. Results: Mean age in the cases in group A is 63.12 years and in group B was 58.24 years with statistically significant difference between the two groups. The duration of the disease and SBP revealed statistically significant difference between the two groups. The LV mass index and E/A ratio revealed high statistically significant difference between the two groups. OPG sequence revealed no statistically significant difference between the two groups, but XRCC3 sequence revealed statistically significant difference. The age was a risk factor for LVH. Conclusion: Osteoprotogrin and XRCC3 genes polymorphism mutations may be associated with left ventricular hypertrophy in hypertensive patients.

The association between RANK, RANKL and OPG gene polymorphisms and the risk of rheumatoid arthritis: a case-controlled study and meta-analysis.

The receptor activator of nuclear factor-κB (RANK) and the osteoprotegerin (OPG) cascade system have been reported to be essential in osteoclastogenesis. In recent years, several studies have investigated the association between polymorphisms of RANK, its ligand RANKL and OPG genes and the risk of rheumatoid arthritis (RA) in different populations. However, the results arising from these studies were conflicting. To determine the association between RANK, RANKL and OPG gene polymorphisms and the risk of RA. We conducted a hospital-based case-controlled study in Changzhou with 574 RA cases and 804 controls. The genotyping of RANK gene rs1805034 polymorphism was conducted by single base extension combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). We also undertook a meta-analysis of the literature referring to polymorphisms of RANK, RANKL and OPG genes and RA risk. This case-controlled study found that the polymorphism in the RANK gene rs1805034 was not related to RA risk. Stratification analyses by sex and age suggested that RANK gene rs1805034 polymorphism was not associated with the risk of RA among groups of male, female, age ≤ 55 and age > 55. Our meta-analysis found that the rs2277438 polymorphism in RANKL gene increased the risk of RA, whereas RANK gene rs1805034, OPG gene rs3102735, OPG gene rs2073618, OPG gene rs3134069 polymorphisms were not related to RA susceptibility. In conclusion, this case-controlled study and meta-analysis indicated that the RANKL gene rs2277438 polymorphism increased the RA risk, and that RANK gene rs1805034, OPG gene rs3102735, OPG gene rs2073618, OPG gene rs3134069 polymorphisms were not related to RA risk.

The genetic association between osteoprotegerin gene polymorphisms and fracture risk in Chinese Han population.

This article put the genetic association exploration of osteoprotegerin (OPG) gene polymorphisms in promoter region (A-163G, T-245G) and fracture risk first and hoped to explain the ethology of fracture. The genotyping of OPG gene polymorphisms was conducted with the method of polymerase chain reaction-restriction fragment length polymorphism in 125 fracture patients and 138 relative controls. The genotype frequencies of selected controls based on OPG gene polymorphisms were checked by the χ2 test whether conformed to Hardy-Weinberg equilibrium (HWE). The relative risk was represented with odds ratio (OR) and 95% confidence interval (95% CI) between gene polymorphism and disease. The linkage disequilibrium (LD) and haplotype were also analyzed. The genotypes distributions of selected controls in OPG polymorphisms conformed to HWE. The G allele of A-163G polymorphism carriers had the tendency to suffer from fracture in the same condition, compared with A allele carriers (OR = 1.63, 95% CI = 1.04-2.55). TG and TG/GG genotypes of OPG T-245G polymorphism also showed the increased risk of fracture development, but not TT genotype (OR = 2.22, 95% CI = 1.15-4.28; OR = 2.45, 95% CI = 1.28-4.68). Likely, the mutant allele G had an abnormally higher frequency in cases than controls (14.00% and 6.16%). These two polymorphisms existed the LD and the haplotype G -163 -G -245 obviously increased the risk of fracture. OPG A-163G, T-245G polymorphisms were associated with the onset of fracture and both the independent risk factors.

The genetic association between osteoprotegerin (OPG) gene polymorphisms and bone mineral density (BMD) in postmenopausal women: A meta-analysis: Erratum.

The genetic association between osteoprotegerin (OPG) gene polymorphisms and bone mineral density (BMD) in postmenopausal women: A meta-analysis: Erratum.

Association of VDR and OPG gene polymorphism with osteoporosis risk in Chinese postmenopausal women

Aims: The underlying mechanisms of vitamin D receptor (VDR) and osteoprotegerin (OPG) genetic variation associated with bone mineral density and osteoporosis remain uncertain. This study aimed to investigate the association of VDR and OPG gene polymorphism as well as gene–gene interaction and their haplotype combination with the risk of osteoporosis.Methods: Polymerase chain reaction restriction fragment length polymorphism was carried out for single nucleotide polymorphism (SNP) detection. Generalized multifactor dimension reduction (GMDR) is used to identify the interaction. SHEsis software evaluated the haplotype and logistic regression was performed to assess the association between the SNPs within the VDR and OPG genes and osteoporosis.Results: The risk of osteoporosis in the VDR-rs2228570 polymorphism T-allele carriers was significantly higher than that in CC (CT/TT versus CC) individuals (adjusted odds ratio [OR] [95% confidence interval (CI)] = 1.76 [1.33–2.22]). The risk of osteoporosis was also higher in the G-allele carrier of the OPG-rs3102735 polymorphism than in individuals with the AA genotype (AG/GG vs. AA) (adjusted OR [95% CI] = 1.65 [1.27–2.14]). However, after adjusting for sex, age, and waist circumference covariates, no significant association of VDR-rs17879735 and OPG-rs2073618 with the osteoporosis risk was revealed. The GMDR method identified that gene–gene interactions were significant, but not for gene/AO interaction. Haplotypes were analyzed with SHEsis software. We did not detect a high-risk haplotype combination associated with osteoporosis.Conclusions: Both VDR-rs2228570-T and OPG-rs3102735-G and their interactions are related to the increased risk of osteoporosis.

The genetic association between osteoprotegerin (OPG) gene polymorphisms and bone mineral density (BMD) in postmenopausal women

Osteoporosis is a common skeletal disorder in eldest people, especially in postmenopausal women. The osteoprotegerin (OPG) gene has been reported to be associated with the BMD and pathogenesis of osteoporosis. However, the results were inconsistent and inconclusive in previous studies. A meta-analysis was performed to investigate the effect of four common OPG gene polymorphisms (A163G, G1181C, T245G, and T950C) on BMD in postmenopausal women. A total of 23 eligible studies with 12,973 postmenopausal women were enrolled in present study. Individuals who with AA genotype of A163G were found to have slightly higher femoral hip (P = .03, SMD = 0.49, [95% CI] = [0.06, 0.91]) and total hip BMD (P = .002, SMD = -0.25, [95% CI] = [-0.42, -0.09]) than those with AG genotype. Subjects with GG genotype of G1181C was found to have lower BMD than those with CC or GC genotypes in lumbar spine (GG vs GC: P = .0002, SMD = -0.85, [95% CI] = [-1.29, -0.41]; GG vs CC: P = .02, SMD = -0.21, [-0.39, -0.03]) and total hip BMD (GG vs GC: P = .002, SMD = -0.25, [95% CI] = [-0.42, -0.09]; GG vs CC: P = .01, SMD = -0.15, [95% CI] = [-0.26, -0.03]). In addition, the subjects with GC genotype of G1181C was detected to have lower BMD than those with CC genotype in lumbar spine BMD (P < .05). Furthermore, individuals with TT genotype of T950C were shown to have significant lower lumbar spine BMD compared with those with genotype CC in Caucasian (P < .05). The lumbar spine BMD was lower for subjects with TC genotype of T950C than those with CC genotype in both Caucasian and Asian populations (P < .05). In contrast to A163G, G1181C, and T950G, no association was detected between T245G polymorphism and BMD (P > .05). The present meta-analysis demonstrated the OPG A163G, G1181C, and T950G, but not T245G, might influence the BMD in postmenopausal women.

Effect of osteoprotegerin gene polymorphisms on the risk of cervical spondylotic myelopathy in a Chinese population

ObjectiveCervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction. Our study aims to explore the correlation of osteoprotegerin (OPG) gene polymorphisms and the risk factors and severity of CSM. Patients and methodsThe peripheral blood samples from 494 CSM patients and 515 healthy individuals were collected for detecting the 950T/C, 1181G/C and 163A/G genotypes and genetic equilibrium of OPG in the CSM and control groups and analyzing the genotype distribution and allele frequency. The severity of CSM and the impaired segments were evaluated by the Japanese Orthopedic Association (JOA) scoring combined with cervical magnetic resonance imaging (MRI), in order to investigate the relations between the three genotypes of OPG promoter gene loci (950T/C, 163A/G and 1181G/C) and occurrence as well as severity of CSM. ResultsThe risk rate of TC genotype carrier suffered from CSM was 0.46, of TT genotype carrier was 0.27. The risk rate of T allele carrier suffered from CSM was 0.37. In 950T/C single nucleotide polymorphism (SNP), patients with TC, TT and T genotypes had lower risk to suffer from CSM. ConclusionTaken together, OPG 950T/C SNP protects against CSM, and it is correlated with the severity of CSM, providing a new idea for the prevention and treatment of CSM.

A meta-analysis on the association between genetic polymorphisms of osteoprotegerin and cardiovascular disease

Objective: To explore the association between genetic polymorphisms of rs2073617T/C (950T/C) and rs2073618G/C(1181G/C) in the osteoprotegerin gene and cardiovascular disease with meta-analysis. Methods: A computer-based search for the study of relationship between genetic polymorphisms of rs2073617T/C and rs2073618G/C in the osteoprotegerin gene and cardiovascular disease were performed in electronic databases including China National Knowledge Infrastructure(CNKI), China Biomedical Literature Database, Wanfang Database, Chinese Journal Full-text Database, Embase, PubMed, and Cochrane Library, supplemented by manual search, from the beginning of library to February 28, 2017. The quality of the included studies were assessed by the Newcastle-Ottawa Scale (NOS) scoring system. Data were analyzed using STATA 12.0 software. Results: Eleven clinical case-control studies that enrolled 2 115 patients with cardiovascular disease and 1 467 healthy subjects were included.The results indicated that osteoprotegerin gene polymorphisms of rs2073617T/C and rs2073618G/C might be closely associated with the susceptibility to cardiovascular disease(rs2073617T/C allele model: OR=0.79, 95%CI 0.73-0.87, P=0.001;rs2073618G/C M allele and W allele: OR=0.83, 95%CI 0.74-0.92, P=0.001). The osteoprotegerin gene polymorphisms of rs2073617T/C and rs2073618G/C were significantly related to the incidence of coronary artery disease and acute coronary syndrome(coronary artery disease allele model: OR=0.83, 95%CI 0.75-0.92, P=0.001; acute coronary syndrome allele model: OR=0.73, 95%CI 0.62-0.85, P<0.001). However, there was no significant correlation between the genetic polymorphisms of these two sites and the lesion vessel number of coronary artery (rs2073617T/C allele model:OR=1.00, 95%CI 0.81-1.24, P=0.985;rs2073618G/C allele model:OR=0.98, 95%CI 0.80-1.21, P=0.626). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-ligase detection reaction(PCR-LDR) evidenced the association between osteoprotegerin gene polymorphisms and cardiovascular disease(allele model: OR=0.79, 95%CI 0.72-0.86, P<0.001), but no obvious relationship was found with fluorogenic quantitative detection and molecularprobe(allele model: OR=0.86, 95%CI 0.65-1.12, P=0.263). Conclusion: This meta-analysis indicates that the osteoprotegerin gene polymorphisms of rs2073617T/C and rs2073618G/C may be closely related to the increased risk of cardiovascular disease.

Relationship between glycemic control and OPG gene polymorphisms with lower bone mineral density in patients with type 1 Diabetes mellitus

ABSTRACT The aim of the present study was to investigate the bone mineral density (BMD) of patients with type 1 Diabetes mellitus (T1DM). We also assessed the association between osteoprotegerin (OPG) genetic polymorphisms and BMD. Genotyping was performed for 1181G>C and 163A>G OPG polymorphisms by allelic discrimination in 119 patients with T1DM and 161 normoglycemic (NG) individuals, aged 6 to 20 years old. Glycemic control, serum parameters of bone metabolism and BMD were evaluated. T1DM patients showed low BMD, poor glycemic control and decreased total calcium values when compared to controls (p < 0.05). For all the polymorphisms studied, the genotype and allele frequencies in patients with T1DM were not significantly different from the controls. In patients with T1DM, carriers of OPG 1181CC showed higher concentrations of ionized calcium compared to patients with GG+GC genotypes. These results suggest that low BMD is associated with poor glycemic control in T1DM. Despite the lack of a detected association between OPG polymorphisms and BMD in these patients, the increased ionized calcium in those carrying OPG 1181CC suggests a possible increase in osteoclastogenesis, a conclusion that may be supported by the lower BMD observed in these subjects.

Association Between Osteoprotegerin Gene Polymorphisms and Risk of Coronary Artery Disease: A Systematic Review and Meta-analysis.

Osteoprotegerin (OPG) has been demonstrated to be a novel biomarker for predicting prevalence and severity of coronary artery disease (CAD). Furthermore, recent studies have shown that OPG gene polymorphisms are associated with a susceptibility to CAD. However, published studies showed inconsistent results. Therefore, a meta-analysis of eligible studies reporting the association between OPG gene polymorphisms and CAD was carried out. A systematic search was conducted using PubMed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and Chinese Wan Fang databases. Odds ratio (OR) with corresponding 95% confidence interval (95% CI) were calculated. Overall, six eligible studies were included and four OPG gene polymorphisms (G209A, T245G, T950C and G1181C) were further evaluated for the association with susceptibility to CAD in this meta-analysis. Meta-analysis showed that G1181C and T950C polymorphisms were strongly associated with the risk of CAD, but no association existed between G209A and T245G polymorphisms and the risk of CAD. In conclusion, our meta-analysis is the first report to estimate the association between OPG gene polymorphisms and susceptibility to CAD. Further large scale case-control studies with rigorous design should be conducted to confirm the above conclusions in the future.