Genetic susceptibility of serum cholesterol and triglyceride in Chinese Han children and adolescents
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ABSTRACT:
SUBMITTER: Zhu W
PROVIDER: S-EPMC3849846 | biostudies-literature | 2013 Jan
REPOSITORIES: biostudies-literature
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Project description:High myopia is a common ocular genetic disease in the world. The study sought to investigate the effect of the Insulin-like growth factor-1 (IGF-1) and Matrix metalloproteinase-9 (MMP-9) genes polymorphisms on high myopia in a Han population of China. This study recruited 216 unrelated Han Chinese subjects, including 103 cases with high myopia and 113 controls. Four tagging single nucleotide polymorphisms (SNPs) of IGF-1 and MMP-9 genes were genotyped using the Sequenom MassARRAY method. The chi-square test showed that the family history was significantly correlated with myopia. The SNP genotypes were all in Hardy-Weinberg equilibrium (P > 0.05). Among the four SNPs, there were statistically significant differences in the genotype and allele frequencies of rs2236416 between the groups (P = 0.024). The significant associations of rs2236416 between cases and controls also appeared after Bonferroni multiple correction (P = 0.024). Then, there were significant differences in the genotypes dominant model and codominant model of rs2236416 between groups (P = 0.007 and P = 0.004, respectively). rs5742632 showed a significant difference between the cases and the controls in the recessive model (P = 0.037). Our findings indicated that rs2236416 of MMP-9 was associated with myopia in the population. The result suggested MMP-9 gene locus may play a role in myopia.
| S-EPMC9123300 | biostudies-literature
Project description:BackgroundAlthough the association between the apolipoprotein A5 (APOA5) genetic variants and hypertriglyceridemia has been extensively studied, there have been few studies, particularly in children and adolescents, on the association between APOA5 genetic variants and obesity or non-high-density lipoprotein cholesterol (non-HDL-C) levels. The objective of this study was to examine whether APOA5 gene polymorphisms affect body mass index (BMI) or plasma non-HDL-C levels in Chinese child population.MethodsThis was a case-control study. Single nucleotide polymorphisms (SNPs) were genotyped using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry for an association study in 569 obese or overweight and 194 healthy Chinese children and adolescents.ResultsGenotype distributions for all polymorphisms in both cohorts were in accordance with the Hardy-Weinberg distribution. The frequencies of the risk alleles in rs662799 and rs651821 SNPs in APOA5 gene were all increased in obese or overweight patients compared to the controls. After adjusted for age and sex, C carriers in rs662799 had a 1.496-fold [95% confidence interval (CI): 1.074-2.084, P = 0.017] higher risk for developing obesity or overweight than subjects with TT genotype, while C carriers in rs651821 had a 1.515-fold higher risk than subjects with TT genotype (95% CI: 1.088-2.100, P = 0.014). Triglyceride (TG) and non-HDL-C concentrations were significantly different among rs662799 variants and both were higher in carriers of minor allele than in noncarriers for TG (1.64 ± 0.96 vs. 1.33 ± 0.67 mmol/L) (P < 0.001), and for non-HDL-C (3.23 ± 0.92 vs. 3.02 ± 0.80 mmol/L) (P = 0.005), respectively. There was also a trend towards increased TG and non-high-density lipoprotein cholesterol levels for rs651821 C carriers (P < 0.001 and P = 0.002, respectively). Furthermore, to confirm the independence of the associations between APOA5 gene and TG or non-HDL-C levels, multiple linear regression analysis was performed and the relationships were not eliminated by adjustment for age, sex and BMI.ConclusionsThese findings suggest the TG-raising genetic variants in the APOA5 gene may influence the susceptibility of the individual to obesity, which may also contribute to an increased risk of high non-HDL-C levels in Chinese obese children and adolescents.
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Project description:Accompanied with nutrition transition, non-HDL-C levels of individuals in Asian countries has increased rapidly, which has caused the global epicenter of nonoptimal cholesterol to shift from Western countries to Asian countries. Thus, it is critical to underline major genetic and dietary determinants. In the current study of 2,330 Chinese individuals, genetic risk scores (GRSs) were calculated for total cholesterol (TC; GRSTC, 57 SNPs), LDL-C (GRSLDL-C, 45 SNPs), and HDL-C (GRSHDL-C, 65 SNPs) based on SNPs from the Global Lipid Genetics Consortium study. Cholesterol intake was estimated by a 74-item food-frequency questionnaire. Associations of dietary cholesterol intake with plasma TC and LDL-C strengthened across quartiles of the GRSTC (effect sizes: -0.29, 0.34, 2.45, and 6.47; Pinteraction = 0.002) and GRSLDL-C (effect sizes: -1.35, 0.17, 5.45, and 6.07; Pinteraction = 0.001), respectively. Similar interactions with non-HDL-C were observed between dietary cholesterol and GRSTC (Pinteraction = 0.001) and GRSLDL-C (Pinteraction = 0.004). The adverse effects of GRSTC on TC (effect sizes across dietary cholesterol quartiles: 0.51, 0.82, 1.21, and 1.31; Pinteraction = 0.023) and GRSLDL-C on LDL-C (effect sizes across dietary cholesterol quartiles: 0.66, 0.52, 1.12, and 1.56; Pinteraction = 0.020) were more profound in those having higher cholesterol intake compared with those with lower intake. Our findings suggest significant interactions between genetic susceptibility and dietary cholesterol intake on plasma cholesterol profiles in a Chinese population.
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Project description:Serum metabolites are potential regulators for chronic diseases. To explore the genetic regulation of metabolites and their roles in chronic diseases, we quantified 2,759 serum metabolites and performed genome-wide association studies (GWASs) among Han Chinese individuals. We identified 184 study-wide significant (p < 1.81 × 10-11) metabolite quantitative trait loci (metaboQTLs), 88.59% (163) of which were novel. Notably, we identified Asian-ancestry-specific metaboQTLs, including the SNP rs2296651 for taurocholic acid and taurochenodesoxycholic acid. Leveraging the GWAS for 37 clinical traits from East Asians, Mendelian randomization analyses identified 906 potential causal relationships between metabolites and clinical traits, including 27 for type 2 diabetes and 38 for coronary artery disease. Integrating genetic regulation of the transcriptome and proteome revealed putative regulators of several metabolites. In summary, we depict a landscape of the genetic architecture of the serum metabolome among Han Chinese and provide insights into the role of serum metabolites in chronic diseases.
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Project description:The association of the rs9939609 single nucleotide polymorphism in FTO gene with obesity has been extensively investigated in studies of populations of European, African, and Asian ancestry. However, inconsistent results have been reported in Asian populations, and the relationship of FTO variation and dietary behaviors has only rarely been examined in Chinese children and adolescents. The aim of this study was to assess the association of rs9939609 with obesity and dietary preferences in childhood in a Chinese population. Epidemiological data including dietary preferences were collected in interviews using survey questionnaires, and rs9939609 genotype was determined by real-time PCR. The associations of rs9939609 genotypes with obesity and dietary preferences were analyzed by multivariate logistic regression using both additive and dominant models. The results showed that subjects with a TA or AA genotype had an increased risk of obesity compared with the TT participants; the odds ratios (ORs) were 1.47 (95% CI: 1.25-1.71, P = 1.73×10-6), and 3.32 (95% CI: 2.01-5.47, P = 2.68×10-6), respectively. After adjusting for age and gender, body mass index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides, and low-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol was lower in TA and AA participants than in those with the TT genotype. After additionally controlling for body mass index, the association remained significant only for systolic blood pressure (P = 0.005). Compared with TT participants, those with the AA genotype were more likely to prefer a meat-based diet (OR = 2.81, 95% CI: 1.52-5.21). The combined OR for obesity in participants with TA/AA genotypes and preference for a meat-based diet was 4.04 (95% CI: 2.8-5.81) compared with the TT participants who preferred a plant-based diet. These findings indicate the genetic variation of rs9939609 is associated with obesity and dietary preferences in Chinese children and adolescents.
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Project description:Dyslipidemia is a major contributor to the increased cardiovascular disease and mortality associated with obesity and type 2 diabetes. We hypothesized that variation in expression of adipose tissue transcripts is associated with serum lipid concentrations in African Americans (AAs), and common genetic variants regulate expression levels of these transcripts. Fasting serum lipid levels, genome-wide transcript expression profiles of subcutaneous adipose tissue, and genome-wide SNP genotypes were analyzed in a cohort of non-diabetic AAs (N=250). Serum triglyceride (TRIG) and high density lipoprotein-cholesterol (HDL-C) levels were associated (FDR<0.01) with expression level of 1021 and 1875 adipose tissue transcripts, respectively, but none associated with total cholesterol or LDL-C levels. Serum HDL-C-associated transcripts were enriched for salient biological pathways, including branched-chain amino acid degradation, and oxidative phosphorylation. Genes in immuno-inflammatory pathways were activated among individuals with higher serum TRIG levels. We identified significant cis-regulatory SNPs (cis-eSNPs) for 449 serum lipid-associated transcripts in adipose tissue. The cis-eSNPs of 12 genes were nominally associated (p<0.001) with serum lipid level in genome wide association studies in Global Lipids Genetics Consortium (GLGC) cohorts. Allelic effect direction of cis-eSNPs on expression of MARCH2, BEST1 and TMEM258 matched with effect direction of these SNP alleles on serum TRIG or HDL-C levels in GLGC cohorts. These data suggest that expressions of serum lipid-associated transcripts in adipose tissue are dependent on common cis-eSNPs in African Americans. Thus, genetically-mediated transcriptional regulation in adipose tissue may play a role in reducing HDL-C and increasing TRIG in serum.
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Project description:Previous studies have demonstrated that integrins are involved in the aetiology of asthma. Several single-nucleotide polymorphisms (SNPs) in the integrin ?3 (ITGB3) gene are significantly associated with asthma in Western populations. Given the important roles of environmental exposures in the development of asthma, we evaluated the associations between six SNPs in ITGB3 and asthma in Chinese Han children. A total of 321 unrelated Chinese children with asthma and 315 healthy children were recruited for the study. SNP genotyping was performed by high-resolution melting analysis (HRM). The selected SNPs were well genotyped by HRM, and SNP rs3809865 in the 3' untranslated region (3'UTR) of ITGB3 was found to be strongly associated with asthma (adjusted p?=?0.004). The minor allele of rs3809865 showed a protective effect against asthma (OR: 0.59; 95% CI: 0.43-0.8). The seed regions of two miRNAs (hsa-mir-124 and hsa-mir-506) were predicted to bind to the sequence containing rs3809865 by TargetScan and PITA. Luciferase reporter assays demonstrated that the T allele of rs3809865 was more efficiently targeted by hsa-mir-124 than was the A allele, which suggested that rs3809865 could affect the binding of hsa-mir-124 to ITGB3. Furthermore, the transfection of A549 cells with hsa-mir-124 resulted in the downregulation of ITGB3 expression. Our results revealed that rs3809865 was significantly associated with asthma due to its effect on the binding of hsa-mir-124 to ITGB3.
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Project description:Objective: The present study was conducted for exploring the influence of fibroblast growth factor 2 receptor (FGFR2) gene polymorphisms on osteoporosis occurrence risk in the Chinese population.Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was conducted for the genotyping of polymorphism in 145 osteoporosis patients and 123 controls. The status of Hardy-Weinberg equilibrium was detected in the control group. Genotype and allele frequency comparison of polymorphism between the two groups was performed by χ2 test, odds ratio (OR) with 95% confidence interval (95% CI) was used for the result expression about the association of FGFR2 polymorphisms with osteoporosis. Furthermore, the results were adjusted by clinical features via logistic regression analysis.Results: AA genotype and A allele of rs2420946 were significantly associated with the increased risk of osteoporosis development adjusted by clinical features (OR = 2.238, 95% CI = 1.055-4.746; OR = 1.482, 95% CI = 1.042-2.019). Similarly, CC genotype and C allele frequencies of rs1219648 were detected the significant difference between the case and control groups (P<0.01); moreover, it was still significant by the adjustion of clinical features, which indicated that rs1219648 was significantly associated with the risk of osteoporosis occurrence (OR = 2.900, 95% CI = 1.341-6.271; OR = 1.602, 95% CI = 1.126-2.279). Haplotype T-A-C-T also obviously increased the occurrence risk of osteoporosis (OR = 1.844, 95% CI = 1.180-2.884). Besides, the significant interaction of FGFR2 polymorphisms with drinking status in osteoporosis was also found (P<0.05), especially rs2981579.Conclusion:FGFR2 rs2420946 and rs1219648 polymorphisms may be the risk factor of osteoporosis in Chinese population. Furthermore, the interaction of FGFR2 polymorphisms with drinking may play an important role in osteoporosis etiology.
| S-EPMC6549083 | biostudies-literature
Project description:The heritability of schizophrenia (SCZ) has been estimated to be as high as 80%, suggesting that genetic factors may play an important role in the etiology of SCZ. Cav1.2 encoded by CACNA1C and Cav1.3 encoded by CACNA1D are dominant calcium channel-forming subunits of L-type Voltage-dependent Ca(2+) channels, expressed in many types of neurons. The CACNA1C has been consistently found to be a risk gene for SCZ, but it is unknown for CACNA1D. To investigate the association of CACNA1D with SCZ, we designed a two-stage case-control study, including a testing set with 1117 cases and 1815 controls and a validation set with 1430 cases and 4295 controls in Han Chinese. A total of selected 97 tag single nucleotide polymorphisms (SNPs) in CACNA1D were genotyped, and single-SNP association, imputation analysis and gender-specific association analyses were performed in the two independent datasets. None was found to associate with SCZ. Further genotype and haplotype association analyses indicated a similar pattern in the two-stage study. Our findings suggested CACNA1D might not be a risk gene for SCZ in Han Chinese population, which add to the current state of knowledge regarding the susceptibility of CACNA1D to SCZ.
| S-EPMC4530443 | biostudies-literature
Project description:BackgroundThe prevention and prediction of sudden cardiac death (SCD) present persistent challenges, prompting exploration into common genetic variations for potential insights. T-box 5 (TBX5), a critical cardiac transcription factor, plays a pivotal role in cardiovascular development and function. This study systematically examined variants within the 500-bp region downstream of the TBX5 gene, focusing on their potential impact on susceptibility to SCD associated with coronary artery disease (SCD-CAD) in four different Chinese Han populations.MethodsIn a comprehensive case-control analysis, we explored the association between rs11278315 and SCD-CAD susceptibility using a cohort of 553 controls and 201 SCD-CAD cases. Dual luciferase reporter assays and genotype-phenotype correlation studies using human cardiac tissue samples as well as integrated in silicon analysis were applied to explore the underlining mechanism.ResultBinary logistic regression results underscored a significantly reduced risk of SCD-CAD in individuals harboring the deletion allele (odds ratio = 0.70, 95% CI [0.55-0.88], p = 0.0019). Consistent with the lower transcriptional activity of the deletion allele observed in dual luciferase reporter assays, genotype-phenotype correlation studies on human cardiac tissue samples affirmed lower expression levels associated with the deletion allele at both mRNA and protein levels. Furthermore, our investigation revealed intriguing insights into the role of rs11278315 in TBX5 alternative splicing, which may contribute to alterations in its ultimate functional effects, as suggested by sQTL analysis. Gene ontology analysis and functional annotation further underscored the potential involvement of TBX5 in alternative splicing and cardiac-related transcriptional regulation.ConclusionsIn summary, our current dataset points to a plausible correlation between rs11278315 and susceptibility to SCD-CAD, emphasizing the potential of rs11278315 as a genetic risk marker for aiding in molecular diagnosis and risk stratification of SCD-CAD.
| S-EPMC10959103 | biostudies-literature