Nutjaree Jeenduang

Combined PCSK9 and APOE Polymorphisms are Genetic Risk Factors Associated with Elevated Plasma Lipid Levels in a Thai Population

Proprotein convertase subtilisin/kexin type 9 (PCSK9) and apolipoprotein E (ApoE) play a key role in the regulation of lipid metabolism. We aimed to investigate the effects of PCSK9 (R46L, I474V, and E670G) and APOE polymorphisms on lipid levels in a Southern Thai population. A total of 495 participants (307 urban, 188 rural) were recruited for the study. Anthropometric and biochemical variables were evaluated. PCSK9 and APOE polymorphisms were analyzed using PCR–RFLP. The 46L urban male carriers had significantly higher diastolic blood pressure (DBP) and fasting blood sugar compared with non-carriers. In contrast, the 46L urban female carriers had significantly lower total cholesterol (TC) and LDL-C levels compared with non-carriers. The 474V rural female carriers had significantly lower HDL-C levels than non-carriers. The 670G urban female carriers showed significantly higher TC and LDL-C levels compared with non-carriers. APOE4 carriers had increased TC and LDL-C levels relative to APOE3 carriers in the urban males. APOE2 carriers had decreased TC and/or LDL-C levels compared with APOE3 carriers in urban males and females. A significant trend of increased TC and LDL-C levels was observed in non-APOE4-PCSK9 670EE carriers to APOE4-PCSK9 670EG carriers in urban subjects. In summary, R46L, I474V, and E670G may be genetic risk factors for cardiovascular disease (CVD) in urban males, rural females, and urban females, respectively. In contrast, R46L had a favorable lipid profiles that may protect against CVD in urban females. The combination of PCSK9 E670G and APOE polymorphisms may represent an independent factor for the determination of lipid levels.

The prevalence of metabolic syndrome in premenopausal and postmenopausal women in Southern Thailand

Abstract Objective: To assess the prevalence of metabolic syndrome (MetS) in premenopausal and postmenopausal women in Southern Thailand. Methods: A cross-sectional study was conducted with 361 healthy women (218 premenopausal women and 143 postmenopausal women) in Southern Thailand. Blood pressure, anthropometric indices, fasting plasma glucose and serum lipid levels were measured. MetS was defined according to criteria of the “National Cholesterol Education Program Adult Panel Treatment III” (NCEP ATPIII). Logistic regression analysis was used to evaluate factors associated with MetS. Results: Waist circumference, systolic blood pressure, diastolic blood pressure, and levels of total cholesterol, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and fasting plasma glucose (FPG) were significantly higher in postmenopausal women, when compared with premenopausal women (p < 0.05). The prevalence of MetS in postmenopausal women (29.37%), was significantly higher than that of premenopausal women (16.97%) (p = 0.005). The most frequent component of MetS in postmenopausal women was central obesity (58.74%), followed by hypertension (58.04%), high triglyceride (27.97%), low HDL-C (23.08%), and high FPG (11.19%). Multivariate analysis revealed that age and higher body mass index (BMI) increased the risk of developing MetS. Conclusion: The prevalence of MetS is higher in postmenopausal women than in premenopausal women, and its significant predictors include age and BMI. Chinese abstract 目的:旨在评估泰国南部绝经前及绝经后妇女代谢综合征（metabolic syndrome,MetS）的流行情况。 方法:在361名泰国南部健康女性中（其中218名绝经前女性，143名绝经后女性）进行横断面调查研究。测定血压、人体测量指标、空腹血糖、血脂水平。MetS诊断根据“全美胆固醇教育计划成人专家治疗组Ⅲ”（National Cholesterol Education Program Adult Panel Treatment Ⅲ,NCEP ATPⅢ）相关标准进行定义。逻辑回归分析用于分析MetS相关因素。 结果:绝经后女性腰围，收缩压，舒张压，以及总胆固醇水平，甘油三酯，低密度脂蛋白，高密度脂蛋白，总胆固醇，空腹血糖水平，较绝经前女性明显升高，差异有统计学意义（p＜0.05）。绝经后女性MetS的发生率（29.63%）要高于绝经前女性（16.97%），差异有统计学意义（p=0.005）。绝经后女性MetS最明显的特征为中心性肥胖（58.74%），其次为高血压（58.04%），高甘油三脂（27.97%），低高密度脂蛋白水平（23.08%），高空腹血糖水平(11.19%)。多变量分析表明年龄以及体重指数（Body mass index,BMI）高增加MetS的发生风险。 结论:绝经后女性MetS的患病率高于绝经前女性，其中年龄以及BMI是有效的预测指标。

Anti-Glycemic and Anti-Hepatotoxic Effects of Mangosteen Vinegar Rind from Garcinia mangostana Against HFD/STZ-Induced Type II Diabetes in Mice

Abstract This study focuses on anti-glycemic and anti-hepatotoxic effects of mangosteen vinegar rind (MVR) on five weeks high-fat diet (HFD) / single dose streptozotocin (STZ) 30 mg/kg BW induced male ICR diabetic mice. Mice were randomly divided into five groups (n=6), normal control, diabetic control, and diabetic groups treated with MVR 100, 200 mg/kg BW and glibenclamide 60 mg/kg BW for one week. After the treatment, lipid profile, glycogen and bilirubin contents, oxidative damage (malondialdehyde, MDA), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT) were measured in plasma and/or liver tissues. MVR and glibenclamide treatment to HFD/STZ-induced diabetic mice significantly reduced their plasma glucose, plasma lipid profile, and hepatic lipid profile (P<0.05). Increased hepatic glycogen content indicates improvement of insulin sensitivity. Moreover, oxidative damage markers were ameliorated in MVR- and glibenclamide-treated groups compared to the diabetic control group. MVR with phenolic compounds content of 75 mg GAE/g dry weight and antioxidant potential of 303 mmol/L Trolox/g dry weight acted as a hepatoprotective agent against oxidative damage.

Association of vitamin D receptor gene polymorphisms with serum 25(OH)D levels and metabolic syndrome in Thai population

Metabolic syndrome (MetS) increases the risk of developing cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The vitamin D receptor gene (VDR) polymorphisms have been found associated with MetS and serum 25(OH)D levels but these associations remain controversial. The aim of this study was to investigate the relationship between the VDR polymorphisms and MetS, metabolic components, and serum 25(OH)D levels within the Thai population. A case-control study included 237 participants with MetS according to the MetS diagnostic criteria of NCEP ATPIII and 376 controls. Anthropometric data, blood pressure, lipid profiles, serum 25 (OH)D, and fasting blood glucose were measured. VDR FokI, BsmI, TaqI, and Cdx2 polymorphisms were genotyped by using PCR-HRM. There were no significant differences in the frequencies of VDR genotypes and alleles between MetS and the control groups. VDR TaqI TT, and BsmI BB + Bb genotypes were associated with lower 25(OH)D levels (p < 0.05) in comparison to TaqI Tt, and BsmI bb genotypes in the MetS group, respectively. In addition, the VDR Cdx2 GG genotype was associated with higher WC compared with the AG genotype in all subjects (p < 0.05). Logistic regression analysis revealed that BB + Bb genotypes of the VDR BsmI had significantly increased the odds ratio (OR) of hypertriglyceridemia when compared with the bb genotype (OR 1.87; 95% CI 1.10-3.19, p = 0.022). In conclusion, VDR BsmI variant was associated with hypertriglyceridemia and may be predisposed to developing MetS. VDR TaqI and BsmI polymorphisms seems to influence serum 25(OH)D levels in MetS subjects, while Cdx2 polymorphism may influence WC in all subjects.

Lack of association between SLCO1B1 polymorphisms and lipid-lowering response to simvastatin therapy in Thai hypercholesterolaemic patients

SLCO1B1 polymorphisms have been reported to affect the responses to statin therapy. However, the association of these polymorphisms and lipid‐lowering responses has been inconsistent.

Quantitative Trait Loci Influencing Hb F Levels in Southern Thai Hb E (HBB: c.79G>A) Heterozygotes

Abstract Variation of fetal hemoglobin (Hb F) expression in heterozygous Hb E (HBB: c.79G>A) individuals is associated with several genetic modifiers and not well understood. This study was undertaken in order to determine the effect of single nucleotide polymorphisms (SNPs), including XmnI Gγ (rs7482144), rs766432 on the BCL11A gene and rs9376074 on the HBS1L gene, on Hb F levels in Southern Thai heterozygous Hb E individuals. A total of 97 Southern Thai subjects carrying heterozygous Hb E were selected for the hematological study. After excluding the samples with α-thalassemia (α-thal) interaction or moderate anemia, because both conditions can affect the hematological parameters, the remaining 74 samples were submitted to SNP analysis. Hematological parameters were measured using an automated hematology analyzer and high performance liquid chromatography (HPLC). The results show that rs766432 was strongly associated with increased Hb F levels and rs7482144 was associated with Hb F levels in each subgroup (genotype) of rs766432. This study suggested that the BCL11A locus has a major effect on Hb F levels compared with the XmnI polymorphism in Hb E heterozygotes. This association of Hb F levels with SNPs is useful for the interpretation of hemoglobin (Hb) typing in heterozygous Hb E samples with high Hb F levels. Future research will need to address the better understanding of the mechanisms of the SNPs that regulate Hb F production without stress erythropoiesis in Hb E heterozygotes.

Hematological and Molecular Characterization of a Novel Hb A2 Variant with Homozygous α-Thalassemia-2 in a Southern Thai Individual

Abstract We report here the hematological and molecular features of a novel δ-globin chain variant found in a Southern Thai woman. Her complete blood count was as follows: red blood cell (RBC) count 5.90 × 1012/L, hemoglobin concentration (Hb) 12.6 g/dL, packed cell volume (PCV) 0.41 L/L, mean corpuscular volume (MCV) 69.5 fL, mean corpuscular Hb (MCH) 21.4 pg, mean corpuscular Hb concentration (MCHC) 30.7 g/dL and RBC distribution width (RDW) 13.1%. The blood smear demonstrated microcytic hypochromic RBCs suggestive of thalassemia trait. Hemoglobin analysis identified Hb A2 + Hb A2-Kiriwong (2.4%) and Hb F (0.1%) on high performance liquid chromatography (HPLC). To characterize the α-thalassemia (α-thal) genotype, common α-thal-1 and α-thal-2 alleles were characterized by multiplex gap-polymerase chain reaction (gap-PCR). The results revealed homozygous α-thal-2 (–α3.7/–α3.7) in this case. DNA sequencing showed the presence of a novel δ-globin gene mutation [δ77(EF1)His→Arg; HBD: c.233A>G] that we named Hb A2-Kiriwong for the village from where the proband lived. In summary, the presence of microcytic hypochromic RBCs in this case was likely the result of the homozygous –α3.7 (rightward) deletion and was not affected by this Hb A2 variant.

APOE and CETP TaqIB polymorphisms influence metabolic responses to 'Hibiscus sabdariffa' L. and 'Gynostemma pentaphyllum' Makino tea consumption in hypercholesterolemic subjects

BACKGROUND AND OBJECTIVES Hibiscus sabdariffa L. (HS) and Gynostemma pentaphyllum Makino (GP) have been used as traditional medicines to treat diabetes and hypercholesterolemia. Nevertheless, there is interindividual variation in the metabolic responses to HS and GP consumption. This may be due to genetic factors. The aim of this study was to investigate the effects of HS and GP tea consumption on anthropometric data, fasting blood glucose (FBG), and lipid concentrations in hypercholesterolemia subjects with different genotypes of the APOE and CETP TaqIB polymorphisms. METHODS AND STUDY DESIGN Forty-eight subjects with hypercholesterolemia were given either HS or GP tea for 30 days. Anthropometric and biochemical variables were determined, and APOE and CETP TaqIB polymorphisms were analyzed using the polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). RESULTS E4 (p=0.008) and homozygous B1B1 (p=0.010) carriers had significantly decreased HDL-C concentrations after HS consumption; in addition, B2 carriers who consumed HS showed significantly decreased triglyceride (TG) concentrations (p=0.039). Regarding GP consumption, non-E4 carriers had significantly decreased HDL-C (p=0.009) and FBG (p=0.042) concentrations. Furthermore, B2 carriers had significantly decreased total cholesterol (TC) (p=0.045), HDL-C (p=0.004), and FBG (p=0.026) concentrations. CONCLUSIONS HS consumption may have beneficial effects with respect to TG concentrations in the B2 carriers, but it may adversely affect HDL-C concentrations in homozygous B1B1 and E4 carriers. In contrast, GP consumption may have favorable effects on TC and FBG concentrations but not on HDL-C concentrations for B2 and/or non-E4 carriers.