Higher triglyceride level predicts hyperuricemia: A prospective study of 6-year follow-up.

BACKGROUND: Despite abundant evidence indicating that higher triglyceride (TG) levels are associated with increased risks of hyperuricemia (HUA), it is unclear whether TG levels can independently predict the incidence of HUA. OBJECTIVE: The aim of the study was to investigate whether TG is an independent risk factor of HUA in a cohort study. METHODS: We explored the relationship between TG levels and HUA in a dynamic cohort established in 2009. During the 6 years of follow-up, 5442 subjects without HUA were studied. We divided subjects into 4 groups based on baseline TG levels and used the Cox hazard regression model to estimate HUA risk by TG quartile, after adjustment for potential confounding factors. Kaplan-Meier survival analysis compared the risk of HUA incidence among individuals in each TG quartile. RESULTS: The incidence of HUA in this cohort was 25.9%. The hazard ratios (95% confidence intervals) for HUA in the second, third, and fourth TG quartiles, compared with the first quartile, were 1.19 (1.01-1.40), 1.33 (1.13-1.57), and 1.62 (1.37-1.92), respectively. The Kaplan-Meier survival analysis suggested that higher TG levels predicted higher incidences of HUA in a dose-dependent relationship. Stratification analyses showed that the association between TG levels and the presence of HUA was more pronounced in individuals aged <50 years, of obese, with normal estimated glomerular filtration rate, and with hypertension. CONCLUSION: Our findings suggest that TG level is a significant and independent risk factor for HUA.

Associations between serum uric acid and the incidence of hypertension: a Chinese senior dynamic cohort study.

BACKGROUND: The prevalence of hyperuricemia has increased dramatically during the past several decades. Studies indicating uric acid is an independent risk factor for hypertension did not sufficiently control for other known risk factors. We explored this relationship in a comprehensive Chinese senior dynamic cohort. METHODS: To investigate the relationship between serum uric acid (SUA) levels and hypertension, we carried out a 6-year retrospective study (2006-2011) in a dynamic cohort with 3591 subjects free of hypertension. The first occasion of documented hypertension per subject was the index event. A Cox proportional hazards model assessed the relationship between SUA and hypertension. Kaplan-Meier survival analysis compared incidence of hypertension among individuals with each SUA quartile. Receiver operating characteristic curves were generated to obtain the area under the curve as a prediction of hypertension from SUA levels. RESULTS: The cumulative prevalence of hypertension in our cohort was 20.7 %. The prevalence of hyperuricemia was 17.5 %. Cox regression analysis showed that, compared with the lowest SUA quartile (<4.69 mg/dl), the 4.69-5.58, 5.58-6.52, and ≥6.52 mg/dl quartiles yielded hazard ratios (95 % confidence intervals) for hypertension of 1.652 (1.265-2.156), 2.195 (1.705-2.825), and 3.058 (2.399-3.899), respectively. Cumulative incidence of hypertension was consistently higher among individuals with hyperuricemia than among those with normal SUA levels. A Kaplan-Meier survival analysis showed that hyperuricemia predicted higher incidences of hypertension in a dose-dependent manner: hypertension onset significantly differed across SUA quartiles. SUA levels were significantly and independently associated with incidence of hypertension in our cohort. CONCLUSIONS: Our results, controlling for known risk factors, suggest that SUA level is an independent risk factor for hypertension and could be a useful indicator of hypertension.

TOX and CDKN2A/B Gene Polymorphisms Are Associated with Type 2 Diabetes in Han Chinese.

To study associations between type 2 diabetes (T2DM) candidate genes and microvascular complications of diabetes (MVCDs), we performed case-control association studies for both T2DM and MVCDs in Han Chinese subjects. We recruited 1,939 unrelated Han Chinese T2DM patients and 918 individuals with normal blood glucose levels as nondiabetic controls. Among T2DM patients, 1116 have MVCDs, 266 have a history of T2DM of >10 years but never developed MVCDs. Eighty-two single-nucleotide polymorphisms (SNPs) in 54 candidate genes were genotyped. Discrete association studies were performed by the PLINK program for T2DM and MVCDs. Significant associations were found among candidate gene SNPs and T2DM, including rs1526167 of the TOX gene (allele A, P = 2.85 × 10(-9), OR = 1.44). The SNP rs10811661 of the CDKN2A/B gene was also associated with T2DM (allele T, P = 4.09 × 10(-7), OR = 1.36). When we used control patients with >10 years of T2DM history without MVCD, we found that the G allele of SNP rs1526167 of the TOX gene was associated with MVCD (nominal P = 4.33 × 10(-4)). In our study, significant associations were found between TOX and CDKN2A/B gene SNPs and T2DM. The TOX polymorphism might account for the higher risk of T2DM and the lower risk of MVCDs in the Han Chinese population.

Polymorphisms in FZD3 and FZD6 genes and risk of neural tube defects in a northern Han Chinese population.

Neural tube defects (NTDs) are the most common and severe malformations of the central nervous system. The association of single nucleotide polymorphisms (SNPs) of the Frizzled 3 (FZD3) and Frizzled 6 (FZD6) genes and NTDs in the Han population of northern China was principally studied. One synonymous SNP (rs2241802) in FZD3 gene and three nonsynonymous SNPs (rs827528, rs3808553 and rs12549394) in FZD6 gene were analyzed by polymerase chain reaction (PCR) and sequencing methods in 135 NTD patients and 135 normal controls. The allele, genotype and haplotype frequencies were calculated and analyzed to examine the relationship between FZD3/FZD6 SNPs and NTDs. Both T allele and TT genotype frequencies of the FZD6 rs3808553 loci in the NTDs group were significantly higher than those in the controls, and children with T allele and TT genotype were associated with increased NTDs risk (OR = 1.575, 95 % CI 1.112-2.230, P = 0.010 and OR = 2.811, 95 % CI 1.325-5.967, P = 0.023, respectively). There were no differences among different genotypes or alleles in other three SNPs. Haplotypes A-G-C and A-T-C in FZD6 were found associated with NTDs in the case-control study (OR = 0.560, 95 % CI 0.378-0.830, P = 0.004 and OR = 1.670, 95 % CI 1.126-2.475, P = 0.011, respectively). The rs3808553 of FZD6 is obviously associated with NTDs in Han population of northern China. The TT genotype may increase risk for NTDs.

GTP cyclohydrolase I and tyrosine hydroxylase gene mutations in familial and sporadic dopa-responsive dystonia patients.

Dopa-responsive dystonia (DRD) is a rare inherited dystonia that responds very well to levodopa treatment. Genetic mutations of GTP cyclohydrolase I (GCH1) or tyrosine hydroxylase (TH) are disease-causing mutations in DRD. To evaluate the genotype-phenotype correlations and diagnostic values of GCH1 and TH mutation screening in DRD patients, we carried out a combined study of familial and sporadic cases in Chinese Han subjects. We collected 23 subjects, 8 patients with DRD, 5 unaffected family members, and 10 sporadic cases. We used PCR to sequence all exons and splicing sites of the GCH1 and TH genes. Three novel heterozygous GCH1 mutations (Tyr75Cys, Ala98Val, and Ile135Thr) were identified in three DRD pedigrees. We failed to identify any GCH1 or TH mutation in two affected sisters. Three symptom-free male GCH1 mutation carriers were found in two DRD pedigrees. For those DRD siblings that shared the same GCH1 mutation, symptoms and age of onset varied. In 10 sporadic cases, only two heterozygous TH mutations (Ser19Cys and Gly397Arg) were found in two subjects with unknown pathogenicity. No GCH1 and TH mutation was found in 40 unrelated normal Han Chinese controls. GCH1 mutation is the main etiology of familial DRD. Three novel GCH1 mutations were identified in this study. Genetic heterogeneity and incomplete penetrance were quite common in DRD patients, especially in sporadic cases. Genetic screening may help establish the diagnosis of DRD; however, a negative GCH1 and TH mutation test would not exclude the diagnosis.