Genes associated with altered serum vitamin D levels in a Chinese population.
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PROVIDER: S-EPMC3913821 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
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Genes associated with altered serum vitamin D levels in a Chinese population.
BoneKEy reports 20130710
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Project description:BackgroundThe goal of this study was to determine if vitamin D receptor (VDR) gene polymorphisms underlie susceptibility to dyslipidemia in a Chinese Han population.MethodsThree tag single nucleotide polymorphisms (SNPs) (rs11574129, rs2228570, and rs739837) were genotyped using TaqMan assays to determine VDR SNP associations with dyslipidemia. We genotyped 877 cases of dyslipidemia from a normotensive, non-diabetes mellitus population and 1822 non-dyslipidemia subjects in a stage I study. In a follow-up stage II study, we included a larger sample of 3124 controls and 1679 cases with dyslipidemia. Finally, we explored the potential molecular mechanism for the SNP associations using molecular modeling analysis.ResultsWe found a significant association between SNP rs2228570 and dyslipidemia in the additive (adjusted odds ratio (OR) = 1.255, 95% Confidence Interval (CI) = (1.118-1.409), P < 0.001), dominant (OR = 1.384, 95% CI = 1.384 (1.136-1.6), P = 0.001) and recessive models (OR = 1.356, 95%CI = 1.1-1.671, P = 0.004) in stage I. We further established that the rs2228570 variant was significantly associated with dyslipidemia in the additive (adjusted OR = 1.146, 95% CI = 1.053-1247, P = 0.002), dominant (OR = 1.184, 95%CI =1.018-1.376, P = 0.028) and recessive models (OR = 1.209, 95%CI = 1.064-1.374, P = 0.004) in stage II. The TT genotype was significantly higher (4.93 ± 0.75 mmol/L) compared to the TC (4.67 ± 0.47 mmol/L) or CC (4.66 ± 0.44 mmol/L) genotype (P = 0.01) in cases with elevated low-density lipoprotein cholesterol (LDL-C) levels. In contrast, the cases with the TT genotype had significantly lower serum 25(OH)D levels (18.43 ± 5.04 ng/ mL) compared to the TC (26.24 ± 4.16 ng/mL) and CC (36.76 ± 8.10 ng/ mL) genotypes (P < 0.001). Multivariable linear regression analysis indicated that the rs2228750 genotype significantly correlated with serum low-density lipoprotein-C (LDL-C) levels in cases with dyslipidemia. Using molecular modeling analysis, we further found that the rs2228570 variant changed the structure and the stability of VDR and altered the binding energy of its ligand.ConclusionsThe VDR rs2228570 variant may increase susceptibility to dyslipidemia in the Chinese Han population.
| S-EPMC6098609 | biostudies-literature
Project description:AimGenome-wide association studies have identified several novel loci associated with serum uric acid concentrations in individuals of European descent. In the current study, we aimed to evaluate the associations between these loci and serum uric acid concentrations in a Chinese population.MethodsFourteen single nucleotide polymorphisms (SNPs) mapped in or near 11 loci (PDZK1, GCKR, LRP2, SLC2A9, ABCG2, LRRC16A, SLC17A1, SLC17A3, SLC22A11, SLC22A12 and SF1) were genotyped in 2329 Chinese subjects in Shanghai. Serum biochemical parameters including uric acid concentrations were determined. All the variants were analyzed for gender differences since uric acid metabolism differed between genders.ResultsIn males after adjustments for age and BMI, GCKR rs780094, SLC2A9 rs11722228 and SF1 rs606458 were associated with the uric acid concentrations, which were statistically significant (P=0.016, 0.001 and 0.03, respectively), whereas SLC2A9 rs3775948 was marginally associated with the uric acid concentrations (P=0.071). In females, SLC22A12 rs506338 was also marginally associated with the uric acid concentrations (P=0.057). The meta-analysis for combined data from both males and females revealed that rs3775948 and rs606458 were associated with the uric acid concentrations (P=0.036 and 0.043, respectively). Furthermore, the gender significantly affected the association of rs11722228 with serum uric acid levels (P=0.012).ConclusionThe SLC2A9 rs11722228, SF1 rs606458 and GCKR rs780094 variants modulate uric acid concentrations in Chinese males, while SF1 rs606458 and SLC2A9 rs3775948 are associated with the uric acid concentrations in both Chinese males and females.
| S-EPMC4220079 | biostudies-literature
Project description:Apolipoprotein E (ApoE), which has been shown to influence serum lipid parameters, can bind to multiple types of lipids and plays an important role in the metabolism and homeostasis of lipids and lipoproteins. A previous study showed that ApoE concentration significantly affects serum lipid levels independently of ApoE polymorphism. The serum lipid levels were also closely correlated with dietary habits, and Shandong cuisine is famous for its high salt and oil contents, which widely differ among the different areas in China. Therefore, studying the effect of ApoE polymorphism on ApoE concentration and serum lipid levels in Shandong province is very important.A total of 815 subjects including 285 men and 530 women were randomly selected and studied from Jinan, Shandong province. In order to evaluate the association of ApoE polymorphism and serum level on lipid profiles, the ApoE genotypes, as well as levels of fasting serum ApoE and other lipid parameters, were detected in all subjects.The frequency of the ApoE E3 allele was highest (83.1%), while those of E2 and E4 were 9.4% and 7.5%, respectively, which are similar to those in other Asian populations. ApoE2 allele carriers showed significantly increased ApoE levels but lower levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and Apolipoprotein B (ApoB).We found that ApoE level is influenced by ApoE polymorphism in a gene-dependent manner. The ApoE polymorphism showed different influences on serum lipid parameters with increasing age and body mass index (BMI) in our Shandong Han population.
| S-EPMC5268055 | biostudies-literature
Project description:The present study aimed to evaluate the influence of serum vitamin D levels on semen quality and testosterone levels. This is a cross-sectional study conducted at Androscience, Science and Innovation Center in Andrology and High-Complex Clinical and Andrology Laboratory in Sao Paulo, Brazil, with 508 male patients, aged 18-60 years, from 2007 to 2017. Seminal parameters and serum sexual hormones were correlated with serum vitamin D concentrations in 260 men selected by strict selection criteria. Patients were divided into normozoospermic group (NZG, n = 124) and a group with seminal abnormalities (SAG, n = 136). Evaluation included complete physical examination, past medical history, habits and lifestyle factors, two complete seminal analysis with sperm functional tests, serum levels of 25-hydroxy-vitamin D3(25(OH)VD3), total and free testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), total cholesterol, homeostatic model assessment of insulin resistance (HOMA-IR) index, and karyotype. The mean concentration of 25(OH)VD3was significantly lower in the SAG (P < 0.001) and positively correlated with all baseline seminal parameters and total testosterone levels. In addition, serum vitamin D3concentration was found to be positively correlated with sperm concentration (β= 2.103; P < 0.001), total number of spermatozoa with progressive motility (β = 2.069; P = 0.003), total number of motile spermatozoa (β = 2.571; P = 0.015), and strict morphology (β = 0.056; P = 0.006), regardless of other variables. This is the first comparative study to address the issue of serum vitamin D3content between normozoospermic patients and those with sperm abnormalities. It clearly demonstrates a direct and positive relationship between serum vitamin D level and overall semen quality, male reproductive potential, and testosterone levels.
| S-EPMC7831823 | biostudies-literature
Project description:Sarcopenia is a geriatric syndrome characterized by progressive loss of muscle mass and function. Heat shock protein (HSP) A12B is essential for angiogenesis and endothelial function. However, the association of HSPA12B levels with sarcopenia remains unclear. A total of 936 community-dwelling elderly people were recruited, and serum HSPA12B was measured by enzyme-linked immunosorbent assay. Appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed were taken to assess sarcopenia. We found that serum HSPA12B levels in patients with sarcopenia (median [interquartile range] = 182.15 [137.58-225.86] ng/mL) were lower than those in elderly people without sarcopenia (228.96 [193.03-292.93] ng/mL, P < 0.001). Receiver operating characteristic curve analysis indicated that the optimal cut-off value of serum HSPA12B level for predicting sarcopenia was 185.50 ng/mL, with a sensitivity of 52.6% and a specificity of 80.8% (area under curve = 0.742, 95% confidence interval [CI] = 0.711-0.772, P < 0.001). Moreover, serum HSPA12B concentration was positively correlated with ASMI (r = 0.354, P < 0.001), grip strength (r = 0.381, P < 0.001), and gait speed (r = 0.169, P < 0.001). Multivariate logistic regression analysis showed that decreased serum HSPA12B levels (<185.50 ng/mL) were a risk factor for increased risk of sarcopenia (adjusted odds ratio = 4.335, 95% CI = 3.136-5.993, P < 0.001). In addition, serum HSPA12B level was also positively correlated with serum levels of angiogenesis markers, vascular endothelial growth factor (r = 0.080, P = 0.014), and angiopoietin-1 (r = 0.108, P = 0.001). In summary, our results indicate that low serum HSPA12B level is associated with an increased risk of sarcopenia in the elderly, suggesting a potential role of HSPA12B in the development of sarcopenia.
| S-EPMC11909431 | biostudies-literature
Project description:Myocardial infarction (MI) is a serious result of coronary artery disease. Recent data from clinical trials have showed that the risk of MI was associated with high plasma apolipoprotein B (apoB) levels. Mutations in ApoB gene were also found to be associated with plasma lipid levels. The aim of this study is to evaluate the effect of ApoB polymorphisms on the risk of MI and plasma apoB levels in a Chinese population. Eight polymorphisms (rs676210, rs679899, rs3791980, rs2854725, rs11676704, rs512535, rs12720841 and rs2678379) in ApoB gene were genotyped in a case-control study in China, including 550 MI cases and 550 healthy controls. Carriers of GG genotype of rs676210 had significant increased risk of MI [odd ratio (OR) = 1.93, 95% confidence interval (CI): 1.23-3.03] compared to carriers of AA genotype. Haplotype analysis also showed that GTTGG (rs676210-rs2854725-rs11676704-rs3791980-rs2678379) haplotype had significant increased risk of MI (OR = 2.82, 95% CI: 1.49-5.33) compared with ATTGA haplotype. Furthermore, apoB rs676210 and rs2678379 polymorphisms were significantly associated with plasma levels of apoB in healthy controls (P = 0.01 and 0.02). Our findings indicated that ApoB mutations may be associated with the risk of MI and plasma ApoB levels in healthy controls in Chinese population.
| S-EPMC4659074 | biostudies-literature
Project description:BackgroundInflammation is one of the major hallmarks of cancer. This study was designed to profile a panel of inflammatory mediators in gastric adenocarcinoma (GA) and to identify their potential differences separately in metastatic and non-metastatic patient subgroups.MethodsSerum samples from 216 GA patients and 333 healthy controls from China were analyzed for six proteins using the Luminex multiplex assay.ResultsThe serum levels for all the six proteins were significantly elevated in metastatic GA compared to non-metastatic GA. Two acute phase proteins (SAA and CRP) and a CXC chemokine (GRO) were significantly elevated in metastatic GA (p <0.01) but smaller changes were observed in non-metastatic GA compared to healthy controls. OPN is moderately increased in non-metastatic GA (2.05-fold) and more severely elevated in metastatic GA (3.34-fold). Surprisingly, soluble VCAM1 and AGP were significantly lower in both non-metastatic and metastatic GA patients compared to controls. Several individual proteins were shown to possess moderate diagnostic value for non-metastatic GA (AUC = 0.786, 0.833, 0.823 for OPN, sVCAM1 and AGP, respectively) and metastatic GA (AUC = 0.931, 0.720, 0.834 and 0.737 for OPN, sVCAM1, SAA and CRP, respectively). However, protein combinations further improve the diagnostic potential for both non-metastatic GA (best AUC = 0.946) and metastatic GA (best AUC = 0.963). The protein combination with best AUC value for both comparisons is OPN+sVCAM1+AGP+SAA.ConclusionsThese results suggest that several serum proteins are directly related to the severity of gastric cancer. Overall, stronger associations are observed with metastatic than non-metastatic GA as the protein changes are greater with the metastatic status. A combination of these serum proteins may serve as non-invasive markers to assess the severity status and stage of gastric cancer.
| S-EPMC4401731 | biostudies-literature
Project description:BACKGROUND: Serum alkaline phosphatase (ALP) is a complex phenotype influenced by both genetic and environmental factors. Recent Genome-Wide Association Studies (GWAS) have identified several loci affecting ALP levels; however, such studies in Chinese populations are limited. We performed a GWAS analyzing the association between 658,288 autosomal SNPs and serum ALP in 1,461 subjects, and replicated the top SNPs in an additional 8,830 healthy Chinese Han individuals. The interactions between significant locus and environmental factors on serum ALP levels were further investigated. RESULTS: The association between ABO locus and serum ALP levels was replicated (P = 2.50 × 10?²¹, 1.12 × 10??? and 2.82 × 10?²? for SNP rs8176720, rs651007 and rs7025162 on ABO locus, respectively). SNP rs651007 accounted for 2.15% of the total variance of serum ALP levels independently of the other 2 SNPs. When comparing our findings with previously published studies, ethnic differences were observed across populations. A significant interaction between ABO rs651007 and overweight and obesity was observed (FDR for interaction was 0.036); for individuals with GG genotype, those with normal weight and those who were overweight or obese have similar serum ALP concentrations; minor allele A of rs651007 remarkably reduced serum ALP levels, but this effect was attenuated in overweight and obese individuals. CONCLUSIONS: Our findings indicate that ABO locus is a major determinant for serum ALP levels in Chinese Han population. Overweight and obesity modifies the effect of ABO locus on serum ALP concentrations.
| S-EPMC3851471 | biostudies-literature
Project description:Background and objectivesSerum alanine aminotransferase (ALT) activity is the most common tool for the assessment of liver diseases. However, it is not clear whether the current normal ALT range really discriminate patients with or without liver diseases. The present study was to establish a new normal range of ALT and examine its ability to identify patients with hepatitis B or nonalcoholic fatty liver disease (NAFLD) in Chinese Han population.Methods53037 adults were included in this study from January 1st 2008 to August 31st 2010. The 95th percentile of ALT in population with relative low risk factors for liver diseases was set as the new upper limits of normal ALT in gender-specific manner.ResultsThe 95(th) percentile levels at low risk factors for liver diseases were achieved at 35 U/L for men and 23 U/L for women. The concordance statistics for detection were 0.873 (95%CI: 0.865-0.881) for HBV and 0.932 (95%CI: 0.927-0.937) for NAFLD in men while 0.857 (95%CI: 0.850-0.864) for HBV and 0.909 (95%CI: 0.903-0.915) for NAFLD in women. The median sensitivity of the current used ALT upper limit (40 U/L) was 6.6% for HBV and 29.7% for NAFLD and median specificity was 98.7% for men and 99.4% for women. Using our new-derived thresholds, the sensitivities ranged from 35.3% to 61.1% and the specificities were 94.8% for men and 94.6% for women.ConclusionsOur results suggest that upper limits of ALT 35 U/L for men and 23 U/L for women in Chinese Han population. Re-consideration of normal limits of ALT should be recommended.Trial registrationChiCTR.org ChiCTR-OCS-11001173.
| S-EPMC3433469 | biostudies-literature
Project description:ObjectivePrevious studies have noted a specific association between type 1 diabetes and insufficient levels of vitamin D, as well as polymorphisms within genes related to vitamin D pathways. Here, we examined whether serum levels or genotypes of the vitamin D-binding protein (VDBP), a molecule key to the biologic actions of vitamin D, specifically associate with the disorder.Research design and methodsA retrospective, cross-sectional analysis of VDBP levels used samples from 472 individuals of similar age and sex distribution, including 153 control subjects, 203 patients with type 1 diabetes, and 116 first-degree relatives of type 1 diabetic patients. Single nucleotide polymorphism (SNP) typing for VDBP polymorphisms (SNP rs4588 and rs7041) was performed on this cohort to determine potential genetic correlations. In addition, SNP analysis of a second sample set of banked DNA samples from 1,502 type 1 diabetic patients and 1,880 control subjects also was used to determine genotype frequencies.ResultsSerum VDBP levels were highest in healthy control subjects (median 423.5 µg/mL [range 193.5-4,345.0; interquartile range 354.1-]586), intermediate in first-degree relatives (402.9 µg/mL [204.7-4,850.0; 329.6-492.4]), and lowest in type 1 diabetic patients (385.3 µg/mL [99.3-1,305.0; 328.3-473.0]; P = 0.003 vs. control subjects). VDBP levels did not associate with serum vitamin D levels, age, or disease duration. However, VDBP levels were, overall, lower in male subjects (374.7 µg/mL [188.9-1,602.0; 326.9-449.9]) than female subjects (433.4 µg/mL [99.3-4,850.0; 359.4-567.8]; P < 0.0001). It is noteworthy that no differences in genotype frequencies of the VDBP polymorphisms were associated with serum VDBP levels or between type 1 diabetic patients and control subjects.ConclusionsSerum VDBP levels are decreased in those with type 1 diabetes. These studies suggest that multiple components in the metabolic pathway of vitamin D may be altered in type 1 diabetes and, collectively, have the potential to influence disease pathogenesis.
| S-EPMC3178281 | biostudies-literature