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Hypertension places a major burden on individual and public health, but the genetic basis of this complex disorder is poorly understood. We conducted a genome-wide association study of systolic and diastolic blood pressure (SBP and DBP) in Amish subjects and found strong association signals with common variants in a serine/threonine kinase gene, STK39. We confirmed this association in an independent Amish and 4 non-Amish Caucasian samples including the Diabetes Genetics Initiative, Framingham Heart Study, GenNet, and Hutterites (meta-analysis combining all studies: n = 7,125, P < 10[sup-6]). The higher BP-associated alleles have frequencies > 0.09 and were associated with increases of 3.3/1.3 mm Hg in SBP/DBP, respectively, in the Amish subjects and with smaller but consistent effects across the non-Amish studies. Cell- based functional studies showed that STK39 interacts with WNK kinases and cation-chloride cotransporters, mutations in which cause monogenic forms of BP dysregulation. We demonstrate that in vivo, STK39 is expressed in the distal nephron, where it may interact with these proteins. Although none of the associated SNPs alter protein structure, we identified and experimentally confirmed a highly conserved intronic element with allele-specific in vitro transcription activity as a functional candidate for this association. Thus, variants in STK39 may influence BP by increasing STK39 expression and consequently altering renal Na[sup+] excretion, thus unifying rare and common BP-regulating alleles in the same physiological pathway. [ABSTRACT FROM AUTHOR]

Obesity is strongly associated with insulin resistance, type 2 diabetes, cardiovascular diseases and dyslipidemia. How these seemingly distinctive diseases cluster together as the metabolic syndrome is a scientifically intriguing and clinically important question, but not well understood. Recent studies indicate that chronic systemic inflammation may be a cause behind the syndrome and that the adipose tissue may contribute to the inflammation since it is not only a storage depot for excess fat, but also is an endocrine organ secreting many polypeptides, known as adipokines. Dysregulation of adipokines may be responsible for the elevation of the inflammatory state in obesity and obesity-associated comorbidities. Numerous studies have investigated the change of adipokines in obesity and diabetes conditions, but the data from Chinese patients are very limited. In this study, we measured the serum levels of several representative adipokines in obese and diabetic Chinese patients treated with rosiglitazone. In non-diabetic subjects, the serum levels of serum amyloid A (SAA), C-reactive protein (CRP) and TNFa in obese people (BMI ≥ 24, n = 24) was significantly higher than the lean subjects (BMI < 24, n = 26, p < 0.01). In contrast, adiponectin levels were significantly lower in the obese group (p < 0.01). On the other hand, no difference in IL-6 and resistin levels was found between the lean and obese groups. Moreover, these adipokines were measured in 34 impaired glucose regulation (IGR) patients and 44 new-onset type 2 diabetes patients (T2D) patients before and after the treatment with rosiglitazone at 4 mg/day for 12 weeks. The rosiglitazone did not change BMI in both groups but decreased fasting glucose and HbA1c levels in the T2D group. The treatment reduced CRP, TNFa and SAA by 11-39% and increased adiponectin by 82% with statistical significance. In conclusion, we found that inflammatory adipokines were elevated in obesity and decreased in diabetics after rosiglitazone treatment, supporting that adipokines may be a mediator in the metabolic syndrome. [ABSTRACT FROM AUTHOR]