SNP rs2073618 of the osteoprotegerin gene is associated with diabetic retinopathy in Slovenian patients with type 2 diabetes.
ABSTRACT: Recent studies indicate that osteoprotegerin (OPG) acts as an important regulatory molecule in the vasculature. Also, a strong association was observed between circulation OPG and microvascular complication. By considering the possible role of OPG in diabetic retinopathy (DR) we examined two of the most studied polymorphisms of the OPG genes rs2073618 (located in exon I) and rs3134069 (located in the promoter region) and their relation to DR in Slovenian patients with type 2 diabetes. Logistic regression analysis demonstrated that the carriers of the CC genotype had a 2.2 higher risk for DR than those with either the CG genotype or the GG genotype (codominant model for rs2073618). Furthermore, the combined effect of single nucleotide polymorphisms (SNPs) rs2073618 and rs3134069 on the DR was stronger than that of each SNP alone. The odds ratio (OR) for individuals with CC genotype (rs2073618) and AA genotype (rs3134069) compared with carriers of CG/GG (rs2073618) + AA (rs3134069) was 2.54 (95% CI = 1.26-5.13, P = 0.01). To conclude, these results indicate that SNPs in the OPG gene may be implicated in the pathogenesis of DR.
Project description:Breast cancer patients treated with aromatase inhibitors (AIs) may experience musculoskeletal adverse events (MS-AEs). Several studies have confirmed that the RANKL/RANK/OPG signaling pathway plays a dominant role in bone health. Therefore, this study aimed to analyze the relationship between the serum levels of RANKL, OPG and their SNPs (single nucleotide polymorphisms) with AI-related MS-AEs.Patients with early stage, hormone-sensitive breast cancer who were receiving AI therapy were enrolled. We included 208 cases with AI-related MS-AEs and 212 without (controls). The levels of estradiol, bone-turnover markers, multiple inflammatory cytokines, RANKL,OPG and lumbar spine BMD were measured, and questionnaires were completed. We analyzed 29 SNPs of RANKL, RANK and OPG using Sequenom MassARRAY assays and PCR-based TaqMan assays. The levels of bone-turnover markers and RANKL and the ratio of RANKL/OPG were higher in patients with AI-related MS-AEs than controls (all p < 0.05). A genetic assay showed that the RANKL SNP rs7984870 and OPG SNP rs2073618 were associated with AI-related MS-AEs. In patients with AI-related MS-AEs, rs7984870 CC and rs2073618 CC were risk genotypes. Carriers of the rs7984870 CC genotype were more likely to have a higher RANKL level and RANKL/OPG ratio than carriers of the GG genotype, and carriers of the rs2073618 CC genotype were more likely to have a lower OPG level and a higher RANKL/OPG ratio than carriers of the GG genotype (all p < 0.05). Moreover, risk genotypes were associated with higher levels of serum CTX and PINP and a lower lumbar spine BMD (all p < 0.05).In conclusion, the RANKL and OPG risk genotypes synergize to negatively impact bone health and predispose breast cancer patients to AI-related MS-AEs.
Project description:BACKGROUND The aim of this study was to investigate the association between T950C (rs2073617) and G1181C (rs2073618) polymorphisms of the osteoprotegerin gene (OPG) and the susceptibility of peri-implantitis in the Chinese Han population. MATERIAL AND METHODS 110 patients with peri-implantitis and 116 healthy persons from the Chinese Han population were included in this study using a case-control design; rs2073617 and rs2073618 in OPG were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The linkage disequilibrium (LD) and haplotype analysis were performed with Haploview software. Hardy-Weinberg equilibrium (HWE) was assessed in the control group based on the genotype distributions of OPG polymorphisms. The genotype, allele, and haplotype distribution differences between the case and control groups were analyzed by chi-square test, and the relative risk of PD was expressed by odds ratio (OR) and 95% confidence interval (CI). RESULTS The study results showed that people carrying the CC genotype of rs2073618 were more likely to have peri-implantitis than GG genotype carriers (OR=2.18, 95% CI=1.03-4.62, p=0.04). In addition, patients with the C allele had 1.47 times the risk of suffering from peri-implantitis (OR=1.47, 95% CI=1.01-2.13, p=0.04), but not rs2073617 polymorphism. The G-C haplotype frequency of rs2073618-rs2073617 in OPG was significantly correlated to the increased susceptibility of peri-implantitis (OR=2.27, 95% CI=1.20-4.30). CONCLUSIONS OPG rs2073618 polymorphism may be related to the risk of peri-implantitis, but not rs2073617. Moreover, haplotype is also a non-ignorable risk factor.
Project description:To investigate the association of several single nucleotide polymorphisms (SNPs) within ACYP2 gene and additional gene- environment interaction with ischemic stroke (IS) risk in a Chinese population.IS risk was significantly higher in carriers with the G allele of rs11896604 than those with CC genotype (CG or GG versus CC), adjusted OR (95%CI) =1.60 (1.18-2.20), and higher in carriers with the A allele of rs12615793 than those with GG genotype (GA or AA versus GG), adjusted OR (95%CI) = 1.66 (1.24-2.15). GMDR model shown a significant two-locus model (p = 0.0010) involving rs11896604 and alcohol drinking, and a significant two-locus model (p = 0.0010) involving rs12615793 and smoking. Current smokers with rs12615793- GA or AA genotype have the highest IS risk, compared to never- smokers with rs12615793-GG genotype, OR (95%CI) = 2.72 (1.64-3.86); current drinkers with rs11896604-CG or GG genotype have the highest IS risk, compared to never- drinkers with rs11896604-CC genotype, OR (95%CI) = 2.51 (1.70-3.40).A total of 1202 participants (660 males, 542 females) were selected, including 600 IS patients and 602 control participants. The mean age of all participants was 68.2 ± 15.8 years. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination. Logistic regression was performed to investigate the impact of 4 SNPs within ACYP2 gene, additional gene-smoking or drinking interaction on IS risk.We found that the G allele of rs11896604 and the A allele of rs12615793 within ACYP2 gene, rs12615793- smoking interaction, and rs11896604-alcohol drinking interaction were all associated with increased IS risk.
Project description:IL-18 polymorphisms influence the transcriptional activity of the IL-18 gene and associated with various diseases. However, their relationships with hepatitis B virus-related liver diseases had not reached a consensus. So we conducted this case-control study with a view to clarifying the association. We included four groups: healthy controls, chronic hepatitis B virus (CHB) carriers, liver cirrhosis (LC) and hepatocellular carcinoma (HCC) groups with each group of 250 persons. Odd ratios (ORs) and 95% confidence intervals (95%CIs) with or without adjustment were calculated. Haplotype analysis was also performed. The results showed people carrying rs187238 CG genotype had a lower risk of LC (CG vs. CC: OR = 0.59, 95%CI = 0.38-0.91, P = 0.02), while GG genotype carriers had a higher risk of HCC (GG vs. CC+CG: OR = 4.73, 95%CI = 1.01-22.1, P = 0.03) than those with CC and CG genotypes in healthy group. Rs187238 GG genotype increased the risk from CHB to LC status (GG vs. CC: OR = 4.81, 95%CI = 1.03-22.6; GG vs. CC+CG: OR = 4.73, 95%CI = 1.01-22.1), meanwhile the trend also existed by controlling confounding factors (GG vs. CC: OR = 6.25, 95%CI = 1.09-35.8; GG vs. CC+CG: OR = 5.91, 95%CI = 1.04-33.7). Haplotype Crs187238Trs1946518 moderately decreased the risk of CHB carriers developing into HCC (OR = 0.69, 95%CI = 0.50-0.96, P = 0.03) after adjustment. In conclusion, IL-18 rs187238 GG genotype may increase the risk of HCC in healthy population and the risk of LC in CHB carriers.
Project description:The receptor activator of nuclear factor-?B (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.
Project description:BACKGROUND: Primary hyperparathyroidism (PHPT) affects mainly cortical bone. It is thought that parathyroid hormone (PTH) indirectly regulates the activity of osteoclasts by means of the osteoprotegerin/ligand of the receptor activator of nuclear factor-κβ (OPG/RANKL) system. Several studies have confirmed that OPG (osteoprotegerin) and RANKL (ligand of the receptor activator of nuclear factor-κβ) loci are determinants of bone mineral density (BMD) in the general population. The aim of this study is to analyze the relationship between fractures and BMD and the rs3102735 (163 A/G), rs3134070 (245 T/G) and rs2073618 (1181 G/C) SNPs of the OPG and the rs2277438 SNP of the RANKL, in patients with sporadic PHPT. METHODS: We enrolled 298 Caucasian patients with PHPT and 328 healthy volunteers in a cross-sectional study. We analyzed anthropometric data, history of fractures or renal lithiasis, biochemical determinants including markers for bone remodelling, BMD measurements in the lumbar spine, total hip, femoral neck and distal radius, and genotyping for the SNPs to be studied. RESULTS: Regarding the age of diagnosis, BMI, menopause status, frequency of fractures or renal lithiasis, we found no differences between genotypes in any of the SNPs studied in the PHPT group. Significant lower BMD in the distal radius with similar PTH levels was found in the minor allele homozygotes (GG) compared to heterozygotes and major allele homozygotes in both OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs in those with PHPT compared to control subjects. We found no differences between genotypes of the OPG rs2073618 (1181 G/C) SNP with regard to BMD in the PHPT subjects. In the evaluation of rs2277438 SNP of the RANKL in PHPT patients, we found a non significant trend towards lower BMD in the 1/3 distal radius and at total hip in the minor allele homocygotes (GG) genotype group versus heterocygotes and major allele homocygotes (AA). CONCLUSIONS: Our study provides the first evaluation of the relationship between SNPs of the OPG/RANK system and sporadic PHPT. Subjects with PHPT and minor homocygote genotype (GG) for the OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs have lower BMD in the distal radius, and this association does not appear to be mediated by differences in PTH serum levels.
Project description:Osteoporosis (OP) is highly prevalent in rheumatoid arthritis (RA) and is influenced by genetic factors. Single-nucleotide polymorphism (SNP) rs2073618 in the <i>TNFRSF11B</i> osteoprotegerin (<i>OPG</i>) gene has been related to postmenopausal OP although, to date, no information has been described concerning whether this polymorphism is implied in abnormalities of bone mineral density (BMD) in RA. We evaluated, in a case-control study performed in Mexican-Mestizo women with RA, whether SNP rs2073618 in the <i>TNFRSF11B</i> gene is associated with a decrease in BMD. RA patients were classified as follows: (1) low BMD and (2) normal BMD. All patients were genotyped for the <i>rs2073618</i> polymorphism by PCR-RFLP. The frequency of low BMD was 74.4%. Higher age was observed in RA with low BMD versus normal BMD (62 and 54 years, resp.; <i>p</i> < 0.001). Worse functioning and lower BMI were observed in RA with low BMD (<i>p</i> = 0.003 and <i>p</i> = 0.002, resp.). We found similar genotype frequencies in RA with low BMD versus RA with normal BMD (GG genotype 71% versus 64.4%, GC 26% versus 33%, and CC 3% versus 2.2%, resp.; <i>p</i> = 0.6). We concluded that in Mexican-Mestizo female patients with RA, the rs2073618 polymorphism of the <i>TNRFS11B</i> gene is not associated with low BMD.
Project description:BACKGROUND Because genotype CG/GG of Furin rs2071410 can increase susceptibility to hypertension, this study investigated whether Furin rs2071410 is correlated with transient ischemic attack (TIA) susceptibility and prognosis. MATERIAL AND METHODS The odds ratios (ORs) and their 95% confidence intervals (95% CIs) were evaluated to assess the association of rs2071410 with TIA risk, and logistic regression was used to estimate the effects of various risk factors (e.g., diabetes, hypertension, and hyperlipidemia) on TIA. RESULTS Compared with the homozygous genotype CC of rs2071410, the frequency of CG + GG genotype in the case group was significantly higher than in the control group (OR=1.47, 95% CI: 1.05-2.05, P<0.05). The CG + GG genotype carriers were observed to have worse 90-day prognosis after TIA treatment than patients carrying CC genotype (OR=12.86, 95% CI: 7.41-22.33, P<0.05). Moreover, logistic regression analysis found that age, diabetes, hypertension, and hyperlipidemia were associated with the onset of TIA (P<0.05, all). Of note, individuals with CG + GG genotype had 49.3% increased risk of TIA compared with individuals with CC genotype (OR=1.49, 95% CI: 1.05-2.12), and patients with CG + GG genotype had worse 90-day prognosis after TIA treatment than patients with CC genotype (OR=11.39, 95% CI: 6.29-20.62). CONCLUSIONS Furin rs2071410 was significantly correlated with TIA occurrence and prognosis in the Chinese population.
Project description:BACKGROUND: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. METHODS: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. RESULTS: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). CONCLUSION:The present meta-analysis demonstrated the OPG A163G, G1181C, and T950G, but not T245G, might influence the BMD in postmenopausal women.
Project description:Diabetic retinopathy (DR) is a common microvascular complication in both type I and type II diabetes. Several previous reports indicated the serum centration of some secretary factors were highly associated with DR. Therefore, we hypothesis regulatory SNPs (rSNPs) genotype in secretary factors may alter these gene expression and lead to DR.At first, pyrosequencing were applying to screen the SNPs which present allele frequency different in DR and DNR. Then individual genotyping was processed by Taqman assays in Taiwanese DR and DNR patients. To evaluate the effect of SNP allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs.We found the frequencies of the CC, CG, and GG genotype of the rs2010963 polymorphism were 15.09%, 47.14%, and 37.74% in DR and 12.90%, 19.35%, and 67.74% in DNR, respectively (p = 0.0205). The prevalence of DR was higher (p = 0.00793) in patients with the CC or CG genotype (62.26% and 32.26% for DR and DNR, respectively) compared with the patients with the GG genotype. To evaluate the effect of rs2010963-C allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs. The rs2010963-C reporter showed 1.6 to 2-fold higher luciferase activity than rs2010963-G in 3 cell lines.Our data proposed rs2010963-C altered the expression level of VEGFA in different tissues. We suggested small increase but long term exposure to VEGFA may lead to DR finally.