Body weight regulation is influenced neuronally via the hypothalamus, which strongly expresses TRPV4. TRPV4 deficiency in mice confers resistance against diet-induced obesity. We investigated the association between TRPV4 gene variants and body mass index (BMI) in Taiwanese subjects. A sample population of 617 Taiwanese subjects was enrolled, and ten TRPV4 gene polymorphisms were selected and genotyped. After adjusting for clinical covariates, significant associations were observed between three studied polymorphisms and BMI using a dominant model (P = 4.83 × 10(-4), P = 1.17 × 10(-4), and P = 3.37 × 10(-4) for rs3742037, rs10735104, and rs3742035, respectively). Obesity as defined according to both the Asian and National Institutes of Health (NIH) criteria was significantly associated with rs10735104 (P = 0.003 and P = 0.037, respectively) in a dominant model. Genotypes at the TRPV4 locus independently affect BMI and obesity status in Taiwanese subjects. This association may broaden our understanding of the role of neuronal influence on body weight regulation. The regulation of TRPV4 channels in skeletal muscle and adipose tissue could also be a new therapeutic target for preventing the development of obesity.
Background
Obesity has become the main health issue in developed countries as it impacts life expectancy and increases mortality of cerebrovascular or cardiovascular diseases. The leptin is one of the adipokines which presents in the serum in proportion to the amount of adipose tissue and is translated from LEP gene. It involves in energy homeostasis, lipid and glucose metabolisms, modulation of immune systems, and thermogenesis. Many previous studies have revealed controversial results between LEP polymorphisms and leptin levels in different ages and ethnicities. Herein, we investigated the impacts of LEP polymorphism against leptin levels in Taiwanese subjects.
Methods
In 599 Taiwanese subjects, excluding clinically overt systemic disease, age below 18 years old, and C‐reactive protein (CRP) level of above 10 mg/L, few of LEP polymorphisms were genotyped with TaqMan SNP genotyping assays, were further analyzed for association with leptin level in univariate and multivariate linear regression analyses with Bonferroni correction for multiple tests in stratified groups. The univariate and stepwise multivariate linear regression analyses were performed to determine the coefficient of determinant of LEP polymorphisms over leptin level.
Results
Significant associations were found between LEP polymorphisms and leptin levels in obese women. Circulating leptin level was positively correlated with inflammatory, insulin resistance markers, and visceral obesity markers in all subjects. Furthermore, stratified and interaction analyses revealed that LEP polymorphisms, rs7799039 and rs2167270, were significantly associated with leptin levels in obese women—8%–10% of which could be explained by LEP polymorphisms.
Conclusion
The LEP polymorphisms are independently associated with leptin levels in Taiwanese obese women. Further, the genetic determinants for leptin levels may be different between obese and nonobese, and in different sex individuals. The obesity status and female sex may exert modification effect on transcription of LEP, particularly in obese women.
evaluated the efficacy and outcome of repetition of DCB for DCB restenosis during a 45-month follow-up.
Methods
Study PopulationThe subjects for this study were derived from the Tzuchi Registry of ENDovascular Intervention for Peripheral Artery Disease (TRENDPAD), which is an ongoing, prospective, physician-initiated, single-center observational registry of patients who underwent EVT for lower limb ischemia that was started in July 2005. This database was searched to identify symptomatic patients who underwent DCB angioplasty for FP disease between March 2013 and September 2014. The details of patient enrollment and exclusion are described elsewhere. 10 The local ethics committee and institutional review board approved this study (IRB E ndovascular therapy (EVT) is the treatment of choice for most patients with symptomatic peripheral arterial disease (PAD). 1 Plain old balloon angioplasty (POBA) with or without stent placement in long femoropopliteal (FP) lesions is associated with high rates of restenosis. 2 Several randomized controlled trials have shown promising results using drug-coated balloons (DCB) without the requirement of metallic implants to treat symptomatic FP disease. 3-6 However, Schmidt et al reported 2-year results of DCB for complex FP lesions with a higher rate of late catch-up restenosis. 7 Iida et al reported that up to 50% of cases required repeated EVT (re-EVT) more than once during the 2-year follow-up among patients who had reintervention for drug-eluting stent (DES) restenosis. 8 Although DCB is effective in the treatment of FP in-stent restenosis (ISR), 9 information regarding the optimal strategy for FP DCB restenosis is lacking. In this study, we
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