Relationships of apelin concentration and APLN T-1860C polymorphism with obesity in Thai children.

BACKGROUND: Childhood obesity represents a serious global health crisis. Apelin and its receptor system are widely distributed throughout the central nervous system and have been demonstrated to serve a role modulating feeding behaviour and energy homeostasis. The purposes of this study were to examine apelin concentrations and anthropometric-cardiometabolic parameters in obese and non-obese children and to identify associations of APLN T-1860C and APLNR G212A polymorphisms with apelin levels and obesity among Thai children. METHODS: This case-control study included an analysis of 325 Thai children: 198 children with obesity and 127 healthy non-obese children. Anthropometric-cardiometabolic variables and apelin concentration were measured. Genotyping of APLN T-1860C and APLNR G212A was performed using the polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: The obese group had significantly lower apelin and HDL-C levels but significantly higher triglycerides and glucose (TyG) index values, TG/HDL-C ratio and TC/HDL-C ratio than the non-obese group (p < 0.01). Apelin level was negatively correlated with body size phenotypes and cardiometabolic parameters (p < 0.05). The APLN T-1860C polymorphism (OR = 4.39, 95% CI = 1.25-15.28) and apelin concentration (OR = 0.45, 95% CI = 0.23-0.92) were significantly associated with obesity among female children (p < 0.05) only, after adjusting for potential covariates. However, the APLNR G212A polymorphism showed no significant relationship with apelin concentration or obesity. CONCLUSION: These findings in Thai children suggest that apelin concentrations are related to obesity and cardiometabolic parameters. Furthermore, the APLN T-1860C polymorphism may influence susceptibility to obesity among female children.

Adipocytokine dysregulation, abnormal glucose metabolism, and lipodystrophy in HIV-infected adolescents receiving protease inhibitors.

BACKGROUND: Lipodystrophy is common in HIV-infected patients receiving protease inhibitors (PIs), stavudine, and zidovudine. Adipocytokines may be altered in lipodystrophy. We evaluated risk factors, adipocytokine levels, insulin resistance, and lipid profiles in HIV-infected adolescents with different lipodystrophy types. METHODS: A cross-sectional study was conducted in 80 perinatally HIV-infected adolescents receiving PI-based highly active antiretroviral therapy for ≥ 6 months. Patients underwent oral glucose tolerance tests and measurements of high-molecular-weight (HMW) adiponectin, leptin, resistin, insulin, and lipids. They were classified into 3 groups based on the clinical findings: no lipodystrophy, isolated lipoatrophy, and any lipohypertrophy (isolated lipohypertrophy or combined type). RESULTS: Of the 80 patients (median age, 16.7 years), 18 (22.5%) had isolated lipoatrophy, while 8 (10%) had any lipohypertrophy (four with isolated lipohypertrophy, and four with the combined type). In a multivariate analysis, longer exposure to stavudine (OR: 1.03; 95% CI, 1.01-1.06; p = 0.005) and indinavir (OR: 1.03; 95% CI, 1.01-1.06; p = 0.012) were associated with lipoatrophy, while longer exposure to didanosine (OR: 1.04; 95% CI, 1.01-1.08; p = 0.017) and indinavir (OR: 1.10; 95% CI, 1.00-1.21; p = 0.045) were associated with any lipohypertrophy. Leptin levels were highest in the any-lipohypertrophy group and lowest in the isolated-lipoatrophy group (p = 0.013). HMW adiponectin levels were significantly lowest in the any-lipohypertrophy group and highest in the no-lipodystrophy group (p = 0.001). There were no significant differences in the levels of resistin among the three groups (p = 0.234). The prevalence of insulin resistance (p = 0.002) and prediabetes/diabetes (p < 0.001) were significantly highest in the any-lipohypertrophy group. Patients with lipoatrophy and those without lipodystrophy had comparable degrees of insulin resistance (p = 0.292). In multiple linear regression analysis, adjusted for age, sex, and waist-height ratio, HMW adiponectin levels were associated with Matsuda index (ß = 0.5; p = 0.003) and quantitative insulin sensitivity check index (QUICKI) (ß = 40.1; p = 0.010) and almost significantly associated with homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.054). Leptin and resistin levels were not associated with HOMA-IR, Matsuda index, or QUICKI (all p > 0.05). CONCLUSIONS: Abnormal glucose metabolism and dysregulation of adipocytokines were common in the HIV-infected adolescents with lipohypertrophy and the combined type. Preventive screening for cardiovascular diseases caused by metabolic alterations should be routinely performed.

Low folate status, and MTHFR 677C > T and MTR 2756A > G polymorphisms associated with colorectal cancer risk in Thais: a case-control study.

Folate plays essential roles in DNA synthesis, repair, and methylation; thus, folate status may affect carcinogenesis. Genetics polymorphisms involved in folate metabolisms have been linked with colorectal cancer (CRC) development. Therefore, we hypothesized that low folate status and related genetic polymorphisms are associated with higher risk of CRC. This case-control study enrolled 105 new cases of CRC, 101 of colorectal adenoma (CRA), and 182 controls from hospitals in Bangkok, Thailand, to examine the association between folate status and methylenetetrahydrofolate reductase (MTHFR) 677C > T, methionine synthase (MTR) 2756A > G, and methionine synthase reductase (MTRR) 66A > G with the risk of CRC and CRA. Regarding CRC risk, the lowest quartile group of serum folate and folate intake had higher risk of CRC than the highest quartile group (odds ratio [OR] = 11.45, 95% confidence interval [CI] = 4.43-29.59) and (OR = 10.29, 95% CI = 4.17-25.41). The lowest quartile group of folate intake also had a higher risk of CRA (OR = 5.22, 95% CI = 2.19-6.09). Low red blood cell folate combined with MTHFR 677C > T polymorphism statistically increased CRC risk (OR = 10.00, 95% CI = 1.36-73.42). Low folate status combined with MTR 2756A > G significantly increased CRA risk (OR = 6.43, 95% CI = 1.38-29.94). Moreover, the risk of CRC was elevated with alcohol consumption and low exercise activity when combined with low folate status (P < .05). This study supported the hypothesis that, in Thais, low folate status is associated with a higher risk of CRC, particularly among those with polymorphisms of the MTHFR 677C > T and MTR 2756 A > G genes.

Associations among serum folate, waist-to-hip ratio, lipid profile, and eating habits with homocysteine in an elderly Thai population.

A lower serum folate level is common in older populations and is associated with increased serum homocysteine concentration. In turn, an elevated homocysteine level is associated with increased risk of cardiovascular disease and age-related diseases. Contemporary studies of folate and dietary risk factors for cardiovascular disease among the elderly population in Thailand are lacking. This cross-sectional study aimed to investigate the relationships among serum folate, homocysteine level, and nutritional status in the elderly Thai. Three hundred individuals, aged 60 years and over, underwent anthropometric and physiological measurements, and biochemical parameters, and eating habits were also determined. Folate insufficiency was found in approximately 35% of subjects. Folate and homocysteine showed a significant inverse correlation. Serum homocysteine levels rose with increasing age. Folate deficiency and high waist-to-hip ratio were associated with 7-fold and 2.5-fold increased risk for hyperhomocysteinemia, respectively. There were positive correlations between homocysteine and waist-to-hip ratio and systolic blood pressure, but a negative correlation between homocysteine and high-density lipoprotein (r = -0.239, p < 0.01), which are markers for cardiovascular disease risk. Folate negatively correlated with body mass index, waist-to-hip ratio, and diastolic blood pressure, but positively with high-density lipoprotein (r = 0.162, p < 0.01). Investigation of eating habits showed that low consumption of green leafy vegetables and high consumption of sugary foods were associated with high homocysteine levels. Given associations between nutritional status and cardiovascular disease confirmed in this study, nutrition education, holistic health promotion, and appropriate behavioral modification of eating habits represent important measures for preventing premature cardiovascular disease in the elderly Thai population.

An adiponectin-S1P axis protects against lipid induced insulin resistance and cardiomyocyte cell death via reduction of oxidative stress.

BACKGROUND: Adiponectin exerts several beneficial cardiovascular effects, however their specific molecular mechanisms require additional understanding. This study investigated the mechanisms of adiponectin action in the heart during high fat diet (HFD) feeding or in palmitate (PA) treated H9c2 cardiomyoblasts. METHODS: 6-week-old male adiponectin knock out (Ad-KO) mice were fed chow or 60% HFD for 6 weeks then received saline or recombinant adiponectin (3µg/g body weight) for an additional 2 weeks. After acute insulin stimulation (4 U/kg), tissue and serum samples were collected for analysis. H9c2 cardiomyocytes were treated ±0.1 mM PA, the adiponectin receptor agonist AdipoRon, or the antioxidant MnTBAP then assays to analyze reactive oxygen species (ROS) production and cell death were conducted. To specifically determine the mechanistic role of S1P, gain and loss of function studies were conducted with adding S1P to cells or the inhibitors THI and SKI-II, respectively. RESULTS: HFD feeding induced cardiac insulin resistance in Ad-KO mice, which was reversed following replenishment of normal circulating adiponectin levels. In addition, myocardial total triglyceride was elevated by HFD and lipidomic analysis showed increased levels of ceramides and sphingosine-1-phosphate (S1P), with only the latter being corrected by adiponectin administration. Similarly, treatment of H9C2 cardiomyoblasts with PA led to a significant increase of intracellular S1P but not in conditioned media whereas AdipoRon significantly increased S1P production and secretion from cells. AdipoRon or the antioxidant MnTBAP significantly reduced PA-induced cell death. Gain and loss of function studies suggested S1P secretion and autocrine receptor activation mediated the effect of AdipoRon to attenuate PA-induced ROS production and cell death. CONCLUSION: Our data establish adiponectin signaling-mediated increase in S1P secretion as a mechanism via which HFD or PA induced cardiomyocyte lipotoxicity, leading to insulin resistance and cell death, is attenuated.

Maoberry (Antidesma bunius) ameliorates oxidative stress and inflammation in cardiac tissues of rats fed a high-fat diet.

BACKGOUND: Chronic fat-rich diets consumption is increased risk associated with cardiovascular diseases (CVD). Prevention or reduction the progression of cardiac tissue deterioration could benefit in CVD. This study aimed to examine the effects of maoberry (Antidesma bunius), a antioxidant-rich tropical fruit, supplementation on oxidative stress and inflammation in cardiac tissues of rats fed a high-fat diet (HFD). METHODS: The male rats orally received HFD with maoberry extract doses of 0.38, 0.76 or 1.52 g/kg or simvastatin (10 mg/kg) for 12 weeks. At the end of the experimental period, the rats were fasted, euthanized and harvested for the hearts. RESULTS: Significantly reduced oxidative stress (malondialdehyde levels) and enhanced antioxidant capacity (ferric-reducing activities) in cardiac tissues of the rats were found. Maoberry extract remarkably ameliorated the expressions of genes involved with pro-inflammatory such as the tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and endothelial nitric oxide synthase (eNOS). CONCLUSIONS: Our findings suggest that maoberry extract has remarkable effects on preventing progression of cardiac tissue deterioration at least through lowering oxidative stress and inflammation.

Correlation of vitamin D binding protein gene polymorphism and protein levels in chronic obstructive pulmonary disease compared with non-chronic obstructive pulmonary disease subjects.

AIM: The risk of vitamin D binding protein (DBP) variations in chronic obstructive pulmonary disease (COPD) compared with non-COPD Thai males were investigated. MATERIALS & METHODS: The rs7041 and rs4588 polymorphisms of the DBP gene and protein level were measured in 136 COPD and 68 non-COPD Thai males. RESULTS: In the COPD group, GC1-1 gave increased forced expiratory volume at 1 s % predicted compared with GC1-2 but with no significant difference. Significantly lower average DBP serum levels were observed in COPD than non-COPD subjects. Positive correlation between serum DBP and forced expiratory volume at 1 s % predicted was observed in non-COPD subjects. DISCUSSION & CONCLUSION: DBP variations might be associated with risk factors in COPD caused by both inflammatory and vitamin D circulation processes.

Impact of a group-based treatment program on adipocytokines, oxidative status, inflammatory cytokines and arterial stiffness in obese children and adolescents.

Background Dysregulation of adipocytokines, inflammatory cytokines and oxidative stress are associated with the pathogenesis of obesity-related complications. This study aimed to evaluate the effect of a group-based lifestyle modification program on adipocytokines, inflammatory cytokines, oxidative status and arterial stiffness in obese youth. Methods A 1-year weight-reduction program was conducted. The program consisted of initial hospitalization and five outpatient group-based sessions held at 1, 2, 3, 6 and 9 months. Pre- and post-intervention measurements included anthropometric data, blood tests, body composition and brachial-ankle pulse wave velocity (ba-PWV). Results A total of 126 obese youths were recruited, and 115 of those completed the study. Twenty-four participants had increased percentage weight for height at the end of the study (group A), 30 had minimal reduction (group B) and 61 had substantial reduction (group C). Lean mass significantly increased in all three groups (all p<0.001). A significant decrease in leptin (group A, p=0.021; group B, p=0.005; group C, p<0.001), interleukin-6 (IL-6) (group A, p=0.019; group B, p=0.004; group C, p<0.001) and ba-PWV (group A, p=0.031; group B, p=0.015; group C, p<0.001) was also observed. No significant change in the oxidative status was found among the groups. Reduction in ba-PWV was correlated with decreases in plasma malondialdehyde (pMDA) (r=0.233, p=0.036) and homeostasis model assessment of insulin resistance (HOMA-IR) (r=0.253, p=0.025). Conclusions A group-based healthy lifestyle program for obese youths had beneficial effects on adipocytokines, inflammatory cytokines and arterial stiffness. Participants without change in weight status also benefited. These improvements may reduce the risk of obese youths developing atherosclerosis.

Vitamin D-binding protein and its polymorphisms as a predictor for metabolic syndrome.

AIM: To investigate the relationship of vitamin D-binding protein (GC) and genetic variation of GC (rs4588, rs7041 and rs2282679) with metabolic syndrome (MetS) in the Thai population. MATERIALS & METHODS: GC-globulin concentrations were measured by quantitative western blot analysis in 401 adults. All participants were genotyped using TaqMan allelic discrimination assays. RESULTS: GC-globulin levels were significatly lower in MetS subjects than in control subjects, in which significant negative correlations of GC-globulin levels with systolic blood pressure, glucose and age were found. Male participants who carried the GT genotype for rs4588 showed an increased risk of MetS compared with the GG wild-type (odds ratio: 3.25; p = 0.004). CONCLUSION: GC-globulin concentrations and variation in GC rs4588 were supported as a risk factor for MetS in Thais.

Yeast ß-Glucan Modulates Inflammation and Waist Circumference in Overweight and Obese Subjects.

Increased inflammation occurs with excessive adiposity and yeast ß-glucan modulates immune responses. This study investigated the potential effect of yeast ß-glucan on inflammatory cytokines in overweight/obese people. A randomized, double blinded, placebo-controlled, clinical trial design enrolled 44 overweight/obese participants with body mass index ≥23 kg/m2, randomized to two groups receiving ß-glucan 477 mg/capsule (n = 22) or placebo (n = 22) orally for six weeks. At weeks one to two, participants received 1 ß-glucan or placebo capsule/day and at four weeks two tablets/day. Anthropometric changes, lipid profiles, liver and renal functions, and inflammatory cytokines were measured. ß-glucan reduced waist circumference (p = 0.037) and blood pressure (p = 0.006) compared with controls after six weeks of intervention. No statistical significance between groups was observed for triglyceride, cholesterol, lipid profile, liver and renal function, or energy and nutrient intake compared with controls at week six. ß-glucan increased interlukin-10 (IL-10), an anti-inflammatory cytokine, by 23.97% from baseline at week two (p < 0.001) and 31.12% at week six (p < 0.001) and was significantly increased compared with controls at week two (p < 0.001) until week six (p < 0.001). ß-glucan reduced pro-inflammatory cytokines IL-6 at week six (p = 0.005) and tumor necrosis factor-α at week two (p = 0.037) compared with controls. Supplementation of yeast ß-glucan for six weeks modulated pro-cytokines that accelerate overweight/obese comorbidities and reduced blood pressure as well as waist circumference, the strong risk factors for cardiovascular disease, in overweight/obese subjects. Thus, ß-glucan might have the potential to decrease comorbid conditions associated with overweight/ obesity.

Low density lipoprotein receptor-related protein 5 gene polymorphisms and osteoporosis in Thai menopausal women.

BACKGROUND: Osteoporosis, characterized by low bone mineral density (BMD) and high bone fracture risk, is prevalent in Thai menopausal women. Genetic factors are known to play a key role in BMD. Low density lipoprotein receptor-related protein 5 (LRP5), a co-receptor in the Wnt/beta-catenin pathway, is involved in many aspects of bone biology. As coding single nucleotide polymorphisms (cSNPs) of LRP5, including A1330V (rs3736228), and Asian-related Q89R (rs41494349) and N740N (rs2306862), are associated with lowered BMD, this study aimed to determine the relationship between these LRP5 polymorphisms and BMD in 277 Thai menopausal women. RESULTS: Only rs3736228 deviated from the Hardy-Weinberg equilibrium of allele frequency (p = 0.022). The median, range and p value for the BMD related to each SNP parameter were compared (Mann-Whitney U test). Significant differences were observed between wild-type and risk alleles for both rs3736228 (total radial, p = 0.011; and radial 33, p = 0.001) and rs2306862 (radial 33: p = 0.015) SNPs, with no significant difference for rs41494349 SNP. Linkage disequilibrium was strong for both rs3736228 and rs2306862 SNPs. Haplotype analysis identified high CC frequency in both normal and osteopenia/osteoporosis groups, with a significant odds ratio for carrying the TT haplotype; however, this was non-significant after adjusting for age. Multivariate binary logistic regression analysis performed for rs3736228 showed that individuals with a body mass index <25 kg/m(2) had an increased risk of osteoporosis for each decade, but the polymorphism had no effect. CONCLUSIONS: This study did not identify LRP5 polymorphisms as a risk factor for osteoporosis in Thai menopausal women. Further studies with larger sample sizes are needed to further clarify the role of LRP5 as a genetic determinant of osteoporosis.

ADIPOQ POLYMORPHISMS AMONG THAIS WITH PRE-DIABETES.

Studies have shown that polymorphisms of adiponectin gene (ADIPOQ) are associated with risk of developing type 2 diabetes mellitus (T2DM). However, no studies have investigated the association between genetic variants of ADIPOQ and pre-diabetes, a group at higher risk for developing T2DM. A total of 75 pre-diabetes and 130 normal subjects were recruited from volunteers in Bangkok, Thailand. Individuals with pre-diabetes were selected based on American Diabetes Association diagnostic criteria. Six ADIPOQ polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism technique. ADIPOQ polymorphism rs266729 C>G is significantly associated with pre-diabetes (p = 0.006). CG/GG genotypes were found among 60% and 40% of pre-diabetes and normal subjects, respectively. SNP rs266729 C>G was associated with increased pre-diabetes risk (OR = 2.64; 95% CI: 1.18-5.89, p = 0.018). No significant differences were found between pre-diabetes and normal subjects for other ADIPOQ polymorphisms. However, haplotype analysis revealed that haplotype GGTAAT is significantly associated with pre-diabetes when compared with GCGAAC reference haplotype (OR = 22.31; 95% CI: 1.37-361.93, p = 0.03). Our data indicate that ADIPOQ rs266729 C>G polymorphism may contribute to the genetic risk of pre-diabetes and provide preliminary data useful in genetic screening for pre-diabetes among Thais.

Prevalence of plasma small dense LDL is increased in obesity in a Thai population.

BACKGROUND: Plasma low density lipoprotein (LDL) particles vary in size, density, electrical charge and chemical composition. An increased presence of small dense LDL (sdLDL), along with raised triglyceride concentrations and decreased high density lipoprotein (HDL) cholesterol concentrations is commonly known as the atherogenic triad and has been observed in some cases of obesity, principally in Europe and America. This study examines the prevalence of sdLDL in the plasma of an obese (BMI≥25 kg/m2) Thai population. METHODS: Plasma from fasted obese (n=48) and non-obese (n=16) Thai participants was subjected to density gradient ultracentrifugation in iodixanol to separate lipoproteins. Gradients were unloaded top-to-bottom into 20 fractions which were assayed for cholesterol, triglyceride, apo B and apo A-1 to identify lipoprotein types and subtypes. RESULTS: LDL cholesterol was subfractionated into LDL I+II (fractions 3-6, ρ=1.021-1.033 g/ml) which was considered to represent large buoyant LDL (lbLDL), LDL III (fractions 7-9, ρ=1.036-1.039 g/ml) which was considered to represent sdLDL, and, LDL IV (fractions 10-12, ρ=1.044-1.051 g/ml) which was considered to represent very sdLDL. Concentrations of LDL III and IV were increased by 15-20% in obese participants whilst that of LDL I+II was concomitantly decreased by 10%. This was accompanied by a 50% increase in plasma triglyceride concentrations and 15% decrease in HDL cholesterol concentrations. Only 3/16 (19%) non-obese participants had a pattern B LDL cholesterol profile (peak density of >1.033 g/ml), whilst 28/48 (58%) obese participants were pattern B. When expressed as a fraction of the LDL concentration, total sdLDL (i.e. LDL III+IV) showed highly significant correlations to plasma triglyceride concentrations and the triglyceride/HDL cholesterol ratio. CONCLUSIONS: The prevalence of sdLDL is increased in obesity in a Thai population such that they demonstrate a similar atherogenic triad to that previously observed in European and American populations.

Metabolomic profiling in liver of adiponectin-knockout mice uncovers lysophospholipid metabolism as an important target of adiponectin action.

Adiponectin mediates anti-diabetic effects via increasing hepatic insulin sensitivity and direct metabolic effects. In the present study, we conducted a comprehensive and unbiased metabolomic profiling of liver tissue from AdKO (adiponectin-knockout) mice, with and without adiponectin supplementation, fed on an HFD (high-fat diet) to derive insight into the mechanisms and consequences of insulin resistance. Hepatic lipid accumulation and insulin resistance induced by the HFD were reduced by adiponectin. The HFD significantly altered levels of 147 metabolites, and bioinformatic analysis indicated that one of the most striking changes was the profile of increased lysophospholipids. These changes were largely corrected by adiponectin, at least in part via direct regulation of PLA2 (phospholipase A2) as palmitate-induced PLA2 activation was attenuated by adiponectin in primary hepatocytes. Notable decreases in several glycerolipids after the HFD were reversed by adiponectin, which also corrected elevations in several diacyglycerol and ceramide species. Our data also indicate that stimulation of ω-oxidation of fatty acids by the HFD is enhanced by adiponectin. In conclusion, this metabolomic profiling approach in AdKO mice identified important targets of adiponectin action, including PLA2, to regulate lysophospholipid metabolism and ω-oxidation of fatty acids.

Associations of Resistin Levels with Resistin Gene Polymorphism and Metabolic Syndrome in Thais.

BACKGROUND: Metabolic syndrome (MS) is a clinical constellation comprising risk factors associated with developing cardiovascular disease and type 2 diabetes. Resistin has been suggested as a linkage between obesity, inflammation and type 2 diabetes. This study aimed to investigate resistin concentrations and hematological-biochemical parameters in MS subjects and controls, and to determine whether two resistin gene (RETN) polymorphisms (-420C>G & +299G>A) are linked to resistin levels and MS among Thais. METHODS: This case-control study was performed with 322 Thai volunteers: 160 MS subjects and 162 controls. Anthropometric parameters and hematological-biochemical variables were determined. The RETN -420C>G (rs1862513) and +299G>A (rs3745367) polymorphisms were genotyped by PCR-RFLP technique. RESULTS: The resistin levels of the MS group were significantly higher than those of the control group. Resistin levels were positively correlated with anthropometric parameters and WBC count in the MS group. According to RETN -420C>G polymorphism, MS subjects with the G allele (CG/GG) (3.9 µg/L) had significantly higher resistin concentrations than in subjects with the CC genotype (2.4 µg/L); with regard to RETN +299G>A polymorphism, carriers with the A allele (GA/AA) (3.8 µg/L) had significantly higher resistin levels than subjects with the GG genotype (2.7 µg/L), after adjusting for potential covariates. However, the RETN -420C>G and +299G>A polymorphisms were not found to be associated with MS, hematological-biochemical parameters and anthropometric variables. CONCLUSIONS: These findings suggest resistin levels are linked with MS and the RETN -420C>G and +299G>A polymorphisms have impacted the circulating resistin concentrations. However, these two RETN polymorphisms probably do not influence susceptibility to MS among Thais.

Common variations in the FTO gene and obesity in Thais: a family-based study.

Several studies have revealed the association between single nucleotide polymorphisms (SNPs) in the first intron of fat mass and obesity-associated (FTO) gene and obesity. To date, more than 100 SNPs in the FTO gene have been identified in various populations. Nevertheless, this association has not yet been confirmed in Thai populations. The aim of this study was to investigate whether FTO variants are associated with obesity in Thais. We analyzed ten variants in the FTO gene (rs9939609, rs9926289, rs8050136, rs9930501, rs9930506, rs9940646, rs9940128, rs1421085, rs17817449, and rs8043757) in 12 families (83 persons); composed of 12 proband cases and 71 associated family members. All participants were genotyped using polymerase chain reaction (PCR) method and DNA sequencing assay. We found significant associations between three SNPs located in the first intron of FTO gene (rs1421085, rs17817449, and rs8043757) and obesity. The odds ratios were 2.82 (95% CI, 1.16-6.90, p=0.02) for rs1421085 and rs17817449, and 3.15 (95% CI, 1.28-7.76, p=0.01) for rs8043757. Strong linkage disequilibrium among ten SNPs was observed (D'>0.8). Haplotype analysis (combination of rs1421085 (T/C), rs17817449 (T/G), and rs8043757 (A/T)) showed that the CGT haplotype is associated with an increased risk of obesity (OR, 2.42; 95% CI, 1.18-4.97; p=0.018) when compared to the reference haplotype (TTA). The SNPs rs1421085, rs17817449 and rs8043757 in the first intron of the FTO gene are associated with increasing risk of obesity in Thais.

Effects of PCSK1 genetic variants on obesity among Thai children and their family members: in relation to health risk, and biochemical and anthropometric parameters.

Single nucleotide polymorphisms (SNPs) in PCSK1, namely, rs6234, rs6235, and rs271939 have been linked to obesity in European population; and rs3811951 has also been connected to type 2 diabetes and obesity parameters in Chinese population. In this family-based case-control study, we analyzed links between PCSK1 genetic variants and obesity in Thai children and their families. Eleven obese children with a percent weight for height > or = 140 who had family history of obesity and 69 family members were recruited. SNPs rs6234, rs6235, rs3811951, and rs271939 of PCSK1 were analyzed using PCR and gene sequencing methods. DNA of 200 normal weight subjects was used as control. Participants with variant genotypes in the rs6234-6235 pair are at significantly more risk of being obese [OR = 2.44 (1.35-4.43), p = 0.003], and also at increased risk of being severely obese (obese class III) [OR = 3.03 (1.20-7.66), p = 0.015]. Variant rs3811951 showed no association with being obese, but is significantly linked to an increased risk of being severely obese [OR = 3.59 (1.42-9.08) p = 0.005]. Moreover, high density lipoprotein (HDL)-C levels between normal and variant rs3811951 group differed considerably, with patients with variant genotype having a lower HDL-C level (p = 0.037). Thus, Thais carrying SNPs rs6234-5 are at increased risk of being obese, and the risk of severe obesity increases when carrying both rs6234-5 and rs3811951, but not with rs271939. Furthermore, patients with genetic variations at rs3811951 are at risk of having low HDL-C levels.

Association of adiponectin gene -11377C>G polymorphism with adiponectin levels and the metabolic syndrome in Thais.

The metabolic syndrome is related to increased risk of developing cardiovascular disease and type 2 diabetes. Adiponectin is an adipocyte-secreted protein with insulin-sensitizing and anti-atherogenic properties. The aims of this study were to evaluate adiponectin levels and biochemical parameters in metabolic-syndrome subjects and healthy controls. The study also sought to identify links between two polymorphisms, -11377C>G (rs266729) and +45T>G (rs2241766) of the adiponectin gene, in relation to adiponectin levels and the metabolic syndrome. Three hundres and thirty-two Thai volunteers: 164 metabolic-syndrome subjects and 168 healthy control subjects were investigated. The adiponectin and HDL-C levels of the metabolic-syndrome group were significantly lower than the control group (p<0.001). Decreased concentration of adiponectin was associated with -11377C>G polymorphism (p<0.001); this polymorphism was significantly more frequent in the metabolic syndrome group than in the control group (p<0.001). However, +45T>G polymorphism of the adiponectin gene was found not to be related to adiponectin level or metabolic syndrome. Therefore, -11377C>G polymorphism was related to the metabolic syndrome susceptibility, and this polymorphism impacted on circulating adiponectin concentrations among Thais.

Measurement of the levels of leptin, BDNF associated with polymorphisms LEP G2548A, LEPR Gln223Arg and BDNF Val66Met in Thai with metabolic syndrome.

BACKGROUND: Metabolic syndrome is a cluster of metabolic risk factors including dyslipidemia, impaired glucose tolerance, hypertension and central obesity. BDNF (Brain-derived neurotrophic factor) and leptin have been implied in the energy homeostasis. The purposes of this study were to examine concentrations of leptin, BDNF and biochemical parameters in metabolic-syndrome subjects and healthy controls, and also to search for associations of leptin gene (LEP) G2548A, leptin receptor gene (LEPR) Gln223Arg, and BDNF gene (BDNF) Val66Met polymorphisms with leptin levels, BDNF levels and metabolic syndrome among Thais. METHODS: The case-controlled design was performed using 322 Thai volunteers (160 metabolic-syndrome subjects; 162 controls) during the health screening program. Metabolic syndrome was assessed by using the modified National Cholesterol Education Program, Adult Treatment Panel III criteria. The levels of leptin, BDNF, insulin, glucose and lipids were measured in samples. Genotyping of LEP G2548A, LEPR Gln223Arg and BDNF Val66Met was carried out using polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: Serum leptin levels were significantly higher in the metabolic-syndrome group than the control group (p < 0.01), but the BDNF difference between them was not significant. Significant associations of LEPR Gln223Arg polymorphism were found with leptin and glucose levels (p < 0.05), after adjusting for potential covariates. This LEPR polymorphism in the metabolic-syndrome group was also significantly more frequent than in the control group (p < 0.05). However, other gene polymorphisms, LEP G2548A and BDNF Val66Met, showed no significant relationship with leptin levels, BDNF levels or metabolic syndrome. CONCLUSION: These findings suggest leptin levels are linked with metabolic syndrome. LEPR Gln223Arg polymorphism impacted leptin concentrations, and this gene polymorphism may influence susceptibility to metabolic syndrome among Thais.

Reduction of atherogenic risk in patients with type 2 diabetes by curcuminoid extract: a randomized controlled trial.

Curcumin is a phytocompound found in the root of turmeric, a common herbal ingredient in many Asian cuisines. The compound contains anti-inflammatory activity, which is mediated through an up-regulation of adiponectin and reduction of leptin. Consumption of curcumin was shown to prevent some deteriorative conditions caused by inflammation, such as ulcerative colitis, rheumatoid arthritis and esophagitis, and so on. Inflammation-associated cardiovascular conditions such as atherosclerosis are common in diabetes patients. The anti-inflammation effect of curcumin might be beneficial to prevent such condition in these patients. We aim to evaluate an antiatherosclerosis effect of curcumin in diabetes patients. Effects of curcumin on risk factors for atherosclerosis were investigated in a 6-month randomized, double-blinded and placebo-controlled clinical trial that included subjects diagnosed with type 2 diabetes. An atherosclerosis parameter, the pulse wave velocity, and other metabolic parameters in patients treated with placebo and curcumin were compared. Our results showed that curcumin intervention significantly reduced pulse wave velocity, increased level of serum adiponectin and decreased level of leptin. These results are associated with reduced levels of homeostasis model assessment-insulin resistance, triglyceride, uric acid, visceral fat and total body fat. In summary, a 6-month curcumin intervention in type 2 diabetic population lowered the atherogenic risks. In addition, the extract helped to improve relevant metabolic profiles in this high-risk population.