Association between the 5-HTR1B gene polymorphisms and alcohol dependence in a Han Chinese population.

The human serotonin receptor 1B (HRT1B) plays an important role in regulating serotonin release. Previous research has suggested that the genetic variation of the HTR1B gene may confer susceptibility to alcoholism or some subtypes of alcohol dependence, but the evidence has been inconsistent. The aim of the present study is to examine whether polymorphic variants of the HTR1B gene are associated with alcohol dependence subtypes or drinking-related behaviors in Chinese Han population. Alcohol-dependent (AD) male patients (n=135) and controls (n=143) were genotyped for two polymorphisms: A161T in the promoter region and the synonymous variation G861C in the coding region of HTR1B. The results showed that the A161T polymorphism was associated with alcohol dependence (T vs. A allele: p=0.002; OR=2.18, 95% CI: 1.32-3.60). This association was strengthened in those with positive family history (OR=3.12, 95% CI: 1.71-5.70) and/or early onset (OR=4.53, 95% CI: 2.18-9.44) of alcohol dependence. The A161T variant was also significantly associated with age of onset of alcoholism (p=0.001). Furthermore, there was a significant difference of haplotypic frequencies between patients and controls (χ(2)=14.84, df=3, p=0.002), with one common haplotype AG of being significantly underrepresented among the patient group compared to the control group (34% vs. 47.7%, permutation p=0.0034; OR=0.56; 95% CI: 0.39-0.79). These findings confirm HTR1B as a susceptibility gene for alcohol dependence in the sample of Chinese Han population. The HTR1B A-161T polymorphism may be particularly valuable as a functional genetic marker for alcoholism and merits additional study.

Beneficial effects of astragalus polysaccharides treatment on cardiac chymase activities and cardiomyopathy in diabetic hamsters.

Over-activation of the local chymase-angiotensin II (Ang II) system has a dominant role in diabetic cardiomyopathy. Astragalus polysaccharides (APS) are used in traditional Chinese medicine to boost immunity. In this study, we investigated the effects of APS treatment on cardiac function, myocardial collagen expression, cardiac ultrastructure, cardiac matrix metalloproteinase (MMP) activity, levels of plasma glycosylated serum protein (GSP), and myocardial enzymes, and the expression of Ang II, chymase, and angiotensin-converting enzyme (ACE) in the diabetic hamster myocardium. Diabetes was induced by a single injection of streptozotocin (60 mg/kg ip). The experimental groups consisted of normal control (n = 15), diabetic (n = 15), insulin-treated diabetic (n = 15, NPH 1-2 U/day ip), and APS-treated diabetic (n = 30, APS 1-2 g/kg/day orally for 10 weeks) hamsters. Diabetic hamsters treated with insulin or APS exhibited significantly decreased blood glucose, plasma GSP, and myocardial enzymes, as well as improvements in cardiac function and cardiac ultrastructure. Compared with insulin treatment, APS treatment significantly reduced myocardial collagen (type I and III) expression and lowered cardiac MMP-2 activity, myocardial Ang II levels, myocardial chymase expression, and p-ERK1/2 kinase expression. In diabetic hamsters, myocardial ACE expression and plasma Ang II levels was not altered by insulin or APS treatment. These results indicate that treatment of diabetic hamsters with APS inhibited the local chymase-Ang II system and improved markers of diabetic cardiomyopathy.