| 1. |
- Wen, Jie, et al.
(författare)
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Investigation of Type 2 Diabetes Risk Alleles Support CDKN2A/B, CDKAL1, and TCF7L2 As Susceptibility Genes in a Han Chinese Cohort
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent genome-wide association studies (GWASs) have reported several genetic variants to be reproducibly associated with type 2 diabetes. Additional variants have also been detected from a metaanalysis of three GWASs, performed in populations of European ancestry. In the present study, we evaluated the influence of 17 genetic variants from 15 candidate loci, identified in type 2 diabetes GWASs and the metaanalysis, in a Han Chinese cohort. Methodology/Principal Findings: Selected type 2 diabetes-associated genetic variants were genotyped in 1,165 type 2 diabetic patients and 1,136 normoglycemic control individuals of Southern Han Chinese ancestry. The OR for risk of developing type 2 diabetes was calculated using a logistic regression model adjusted for age, sex, and BMI. Genotype-phenotype associations were tested using a multivariate linear regression model. Genetic variants in CDKN2A/B, CDKAL1, TCF7L2, TCF2, MC4R, and PPARG showed a nominal association with type 2 diabetes (P <= 0.05), of whom the three first would stand correction for multiple testing: CDKN2A/B rs10811661, OR: 1.26 (1.12-1.43) P = 1.8* 10(-4); CDKAL1 rs10946398, OR: 1.23 (1.09-1.39); P = 7.1* 10(-4), and TCF7L2 rs7903146, OR: 1.61 (1.19-2.18) P = 2.3* 10(-3). Only nominal phenotype associations were observed, notably for rs8050136 in FTO and fasting plasma glucose (P = 0.002), postprandial plasma glucose (P = 0.002), and fasting C-peptide levels (P = 0.006) in the diabetic patients, and with BMI in controls (P = 0.033). Conclusions/Significance: We have identified significant association between variants in CDKN2A/B, CDKAL1 and TCF7L2, and type 2 diabetes in a Han Chinese cohort, indicating these genes as strong candidates conferring susceptibility to type 2 diabetes across different ethnicities.
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| 2. |
- Yang, Zhen, et al.
(författare)
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Elevated Serum Chemokine CXC Ligand 5 Levels Are Associated with Hypercholesterolemia But Not a Worsening of Insulin Resistance in Chinese People.
- 2010
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 3926-3932
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Recent study showed high chemokine CXC ligand 5 (CXCL5) is thought to be associated with insulin resistance in humans. However, evidence from large-scale populations about the relationship between serum CXCL5 level and metabolic phenotypes is scarce. Here we sought to evaluate serum CXCL5 distribution and its association with metabolic phenotypes among middle-aged and older Chinese. Research Design and Methods: We evaluated serum CXCL5 in a cross-sectional sample of 3225 Chinese aged from 50 to 88 yr in a Shanghai downtown district by ELISA. Glucose, insulin, lipid profile, inflammatory marker, and adipokine were also measured. Results: The crude mean of serum CXCL5 concentrations were 1493.31 pg/ml for men and 2059.42 pg/ml for women (P < 0.001), respectively. After multiple adjustment, the odds ratios were substantially higher for hypercholesterolemia (odds ratio 3.26, 95% confidence interval 2.36-4.51) in the highest CXCL5 quartile compared with those in the lowest quartile. These associations remained significant after further adjustment for body mass index, body fat, inflammatory marker, and adipokine. However, serum resistin CXCL5 was not associated with body mass index, percent body fat, fasting glucose, insulin levels, and homeostasis model assessment index-insulin resistance (r = 0.01, 0.01, 0.01, 0.04, and 0.03, respectively; all P > 0.05). Conclusions: Elevated circulating CXCL5 concentrations were associated with higher risk of hypercholesterolemia in middle-aged and elderly Chinese independent of obesity, inflammation, adipokines, and other risk factors but not insulin resistance.
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| 3. |
- Yang, Zhen, et al.
(författare)
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Genetic variation in the GCKR gene is associated with non-alcoholic fatty liver disease in Chinese people
- 2011
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 38:2, s. 1145-1150
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies reported that GCKR rs780094 polymorphism is associated with elevated fasting serum triglyceride levels and elevated levels of C-reactive protein (CRP). There are a ample of data on the association between circulating triglyceride, CRP concentrations and risk of non-alcoholic fatty liver (NAFLD). To determine whether the GCKR rs780094 polymorphism contributes to the development of non-alcoholic fatty liver, a case-control study was performed in 903 Chinese subjects. Among study population, 436 patients with B-mode ultrasound-proven NAFLD (318 with steatosis hepatis IA degrees, 90 with steatosis hepatis IIA degrees and 28 with steatosis hepatis IIIA degrees) and 467 controls were genotyped by using TaqMan allelic discrimination assays. We confirmed the association of GCKR rs780094 with NAFLD in Chinese people (OR = 1.607, 95% CI 1.139-2.271, P ([dom]) = 7.2 x 10(-3)). In this study, polymorphism in GCKR rs780094 was not significantly associated with the degree of fatty infiltration of the liver. In addition, the T-allele of GCKR rs780094 was significantly associated with increasing fasting triglyceride (P ([add]) = 3.8 x 10(-4)) and CRP (P ([add]) = 2.9 x 10(-4)) concentrations after adjusting for age, gender, and BMI. The association with NAFLD remained significant after adjustment for triglyceride, while adjustment for CRP abolished the association. Genetic variation in GCKR gene rs780094 polymorphism contributes to the risk of NAFLD in Chinese people. The effect of genotype on NAFLD is probably mediated through chronic low-grade systemic inflammation rather than through dislipidemia.
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| 4. |
- Yang, Zhen, et al.
(författare)
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PPARG gene Pro12Ala variant contributes to the development of non-alcoholic fatty liver in middle-aged and older Chinese population
- 2012
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 348:1, s. 255-259
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress has been suggested to contribute to the development of non-alcoholic fatty liver disease (NAFLD). Peroxisome proliferator-activated receptor gamma (PPAR-gamma) heterozygous mice and Pro12Ala (C/G) polymorphism in PPARG exhibited increased resistance to oxidative stress. Smoking increases the production of reactive oxygen species, which could accelerates oxidative stress under overnutrition. To explore whether the C/G polymorphism, alone or in combination with smoking, may promote the development of non-alcoholic fatty liver, a case-control study was performed in 903 Chinese subjects. Among the study population, 436 patients with B-mode ultrasound-proven NAFLD (318 with steatosis hepatis I degrees, 90 with steatosis hepatis II degrees and 28 with steatosis hepatis III degrees) and 467 controls were genotyped by using TaqMan allelic discrimination assays. After adjusting for confounders, the C/C genotype significantly associated with NAFLD (OR = 1.87, 95%CI 1.13-2.85, p = 0.009); smoking was also an independent risk factor for NAFLD (OR = 1.69, 95%CI 1.18-2.43, p = 0.025). In addition, we found possible synergistic effects, the higher risk group (smokers with the C/C genotype) showed 3.75 times higher risk of NAFLD than the low-risk group (non-smokers with C/G genotype) in a multiple logistic analysis after adjusting for the confounders (p < 0.001), but no departure from additivity was found. Our results indicated that the C/C genotype and smoking were significant independent risk factors for NAFLD. The possible synergistic effects of genotype and smoking may promote the development of NAFLD by aggravating oxidative stress, which supports the hypothesis that oxidative stress contributes to the development of NAFLD. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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| 5. |
- Yang, Zhen, et al.
(författare)
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Prevalence of non-alcoholic fatty liver disease and its relation to hypoadiponectinaemia in the middle-aged and elderly Chinese population
- 2011
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Ingår i: Archives of Medical Science. - : Termedia Sp. z.o.o.. - 1734-1922. ; 7:4, s. 665-672
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Hypoadiponectinaemia is an important risk factor for non-alcoholic fatty liver disease (NAFLD). However, little is known about its role in the Chinese population. This study sought to assess the prevalence of NAFLD and its association with hypoadiponectinaemia in middle-aged and elderly Chinese. Material and methods: We conducted a population-based cross-sectional study in an urban Shanghai sample of 2201 participants age 50 years to 83 years (973 men, 1228 women). Hepatic ultrasonographic examination was performed for all participants. Serum adiponectin concentrations were measured by ELISA methods. Results: The prevalence of NAFLD was 19.8% (16.0% in men, 22.8% in women). Serum adiponectin levels were significantly higher in female than in male subjects (p < 0.001). Serum adiponectin levels were significantly lower in NAFLD subjects than those in control subjects (p < 0.001). The prevalence of NAFLD progressively increased with declining adiponectin levels (p(for) (trend) < 0.001). The participants in the lowest adiponectin quartile had a significantly increased risk for acquiring NAFLD (OR = 2.31, 95% CI 1.72-3.15) after adjustment for potential confounders. Conclusions: Population-based screening suggests that NAFLD is highly prevalent in middle-aged and elderly people in Shanghai, particularly among women. Serum adiponectin level is negatively associated with NAFLD independently of potential cofounders, indicating that hypoadiponectinaemia may contribute to the development of NAFLD.
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