High-density lipoprotein size distribution can differ between subjects with alcoholic and non-alcoholic fatty liver disease.

BACKGROUND: While alcohol consumption is associated with levels of high-density lipoprotein (HDL)-cholesterol (HDL-C), a cardiovascular risk marker, HDL size distribution has yet to be characterized in subjects with alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD). METHODS: The present study compared HDL subfractional characteristics between subjects with AFLD (36 men, age 61 +/- 14) and NAFLD (35 men, age 65 +/- 13), recruited during general health check-ups. Serum HDL subfractions were measured with the electrophoretic separation of lipoproteins employing the Lipoprint system. RESULTS: The subjects with AFLD had a significantly greater proportion of small-sized HDL part (6.6 +/- 5.7%) than those with NAFLD (3.8 +/- 4.9%, p = 0.029). CONCLUSIONS: More percentages of small-sized HDL part were observed in the subjects with AFLD than in those with NAFLD in Japanese general population. Whether the difference of HDL size is associated with cardiovascular manifestations should be studied further.

Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1), a nationwide cluster randomized trial of type 2 diabetes prevention by telephone-delivered lifestyle support for high-risk subjects detected at health checkups: rationale, design, and recruitment.

BACKGROUND: Lifestyle modifications are considered the most effective means of delaying or preventing the development of type 2 diabetes (T2DM). To contain the growing population of T2DM, it is critical to clarify effective and efficient settings for intervention and modalities for intervention delivery with a wide population reach.The Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1) is a cluster randomized controlled trial to test whether goal-focused lifestyle coaching delivered by telephone can prevent the development of T2DM in high-risk individuals in a real-world setting. This paper describes the study design and recruitment of the study subjects. METHODS: For the recruitment of study subjects and their follow-up annually over 3 years, we employed health checkups conducted annually at communities and worksites. Health care divisions recruited from communities and companies across Japan formed groups as a cluster randomization unit. Candidates for the study, aged 20-65 years with fasting plasma glucose (FPG) of 5.6-6.9 mmol/l, were recruited from each group using health checkups results in 2006. Goal-focused lifestyle support is delivered by healthcare providers via telephone over a one-year period. Study subjects will be followed-up for three years by annual health checkups. Primary outcome is the development of diabetes defined as FPG≥7.0 mmol/l on annual health checkup or based on self-report, which is confirmed by referring to medical cards. RESULTS: Forty-three groups (clusters), formed from 17 health care divisions, were randomly assigned to an intervention arm (22 groups) or control arm (21 clusters) between March 2007 and February 2008. A total of 2840 participants, 1336 from the intervention and 1504 from the control arm, were recruited. Consent rate was about 20%, with no difference between the intervention and control arms. There were no differences in cluster size and characteristics of cluster between the groups. There were no differences in individual characteristics between the study arms. CONCLUSION: We have launched J-DOIT1, a nation-wide trial to prevent the development of T2DM in high-risk individuals using telephone-delivered intervention. This trial is expected to contribute to evidence-based real-world preventive practices. TRIAL REGISTRATION: UMIN000000662.

The association of the Clock 3111 T/C SNP with lipids and lipoproteins including small dense low-density lipoprotein: results from the Mima study.

BACKGROUND: The clock molecule plays major roles in circadian rhythmicity and regulating lipid and glucose metabolism in peripheral organs. Disruption of the circadian rhythm can lead to cardiometabolic disorders. The existence of small dense low-density lipoprotein (sdLDL) in the circulation, an abnormality of lipid metabolism, in part associated with lifestyle, is also one of risk parameters for cardiometabolic disorders. The 3111 T/C single nucleotide polymorphism (SNP) of the Clock gene has been reported to be associated with lifestyle including morning/evening preference. We investigated whether the Clock 3111 T/C SNP may affect lipids and lipoproteins including sdLDL. METHODS: In 365 community-dwelling subjects (170 men and 195 women, mean age 63 ± 14 years), the 3111 T/C SNP was genotyped using a fluorescent allele-specific DNA primer assay system. The levels of sdLDL were measured with the electrophoretic separation of lipoproteins employing the Lipoprint system. RESULTS: The frequency of the Clock 3111 C allele was 0.14. The area of sdLDL did not differ between the subjects with obesity and those without. In carriers of T/T homozygotes, the area of sdLDL was significantly higher compared with carriers of the C allele (T/C or C/C) (1.7 ± 3.4 vs. 0.8 ± 1.9%; p < 0.05). A multiple regression analysis showed that the area of sdLDL was significantly and negatively correlated with the Clock 3111 T/C SNP (ß = -0.114, p < 0.05), independently of age, sex, body mass index, and exercise habits. CONCLUSION: Our findings indicated that the Clock 3111 T/C SNP might be associated with the existence of sdLDL.

The improvement of sweet taste sensitivity with decrease in serum leptin levels during weight loss in obese females.

Leptin may influence sweet taste sensitivity. However, there are no reports on an association between the sweet taste threshold and serum leptin levels during weight loss in humans. We investigated the changes in the sweet taste threshold and the serum leptin levels during a weight-loss program, in connection with a leptin receptor polymorphism (Lys109Arg) that may be related to insulin and glucose metabolism. The study included 20 obese, but otherwise healthy, females (mean age: 55 +/- 7 years, body mass index: 26.1 +/- 1.7 kg/m(2)). Participants completed a 12-week weight-loss program based on energy restriction through diet and exercise, which aimed at achieving their optimal weight. The sweet taste threshold was determined according to the whole-mouth gustatory method. Genetic analyses were performed using the allele-specific DNA assay. Serum leptin levels were decreased from 9.2 +/- 4.5 to 7.9 +/- 4.9 ng/ml (p = 0.014) after body weight loss. The sweet taste threshold also decreased significantly from 0.59 +/- 0.42 to 0.22 +/- 0.20% in a solution of sucrose (p = 0.004). In contrast, there were no differences in changes of the threshold between participants with and without the Lys109 allele. A multiple regression analysis revealed that the changes in serum leptin levels were significantly correlated with those in the sweet taste threshold, independent of the initial threshold levels and the Lys109 allele. In conclusion, the serum leptin levels are decreased significantly during a weight-loss program in obese females, which may be associated with the decrease in the sweet taste threshold.

The Smart Life Stay (SLS) program: effects of a lifestyle intervention program in combination with health tourism and health guidance for type 2 diabetes.

BACKGROUND: The aim of this study was to determine the effectiveness of the Smart Life Stay (SLS) program, which is an experience-oriented stayover program, in combination with health tourism and mandatory health guidance on glucose metabolism after 2 years. METHODS: The participants of the SLS program (n = 792) were recruited from a database of 23 medical insurers. They underwent a mandatory health examination termed Specific Health Checkups in 2014. The participants were included if they had diabetes or were at a high risk of diabetes and if they satisfied the following inclusion criteria: (1) body mass index (BMI; kg/m2) > 25, or (2) waist circumference (WC; cm) > 85 for men and > 90 for women, or (3) hemoglobin A1c (HbA1c; %) > 5.6, or (4) fasting plasma glucose (FPG; mg/dl) > 100. Individuals who corresponded to one or more items were included as study participants. The control subjects (n = 3645) were nonparticipants of the program who were selected from the database and met the inclusion criteria. The lifestyle changes and changes in mean BMI, WC, FPG, and HbA1c in both groups from baseline to 2-year follow-up were compared by inverse probability weighting of a propensity score. RESULTS: The percentage of people who exercised regularly increased significantly in the SLS group compared with the control group. In the SLS group, BW, BMI, and WC significantly decreased by 1.75 kg, 0.60 kg/m2, and 1.45 cm, respectively, whereas in the control group, WC, FPG, and HbA1c increased significantly by 0.38 cm, 3.37 mg/dl, and 0.12%, respectively. The comparison between groups revealed that the BW, BMI, WC, FPG, and HbA1c improved significantly in the SLS group. CONCLUSIONS: The SLS program is suggested to help improve glucose metabolism. This program could be a feasible option as a lifestyle intervention program for diabetes.

Correction: The Smart Life Stay (SLS) program: effects of a lifestyle intervention program in combination with health tourism and health guidance for type 2 diabetes.

Following publication, the authors asked to add the following institution to the affiliations of author Madoka Matsushita: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Both the PDF and HTML versions of the Article have been updated accordingly.

An association between angiotensin II type 2 receptor gene A/C3123 polymorphism and glycemic control marker in a general Japanese population.

Objective Angiotensin II (Ang II), through the Ang II type 2 receptor (AT2R), may play some roles in the pathogenesis of glucose metabolism and diabetes mellitus (DM). The Adenine/Cytosine 3123 (A/C3123) polymorphism in the AT2R gene has reportedly been associated with metabolic conditions such as blood pressure and body mass index (BMI). The present cross-sectional study was aimed at investigating the association between the AT2R gene A/C3123 polymorphism and glycemic control parameters. Methods Among 286 community-dwelling Japanese subjects (men: women = 126:160; mean age, 65.1 years), AT2R A/C3123 polymorphism, which was detected by polymerase chain reaction methods, and metabolic parameters such as blood pressure, BMI, lipoprotein/lipid, insulin, and glycemic control parameters (fasting plasma glucose and HbA1c) were examined. Results In the whole study population, the proportion of C-allele was 67.0% and A-allele was 33.0%. The A-allele carriers had significantly lower HbA1c levels than the C/C-genotyped subjects in the group of women (5.5 +/- 0.6 vs. 5.8 +/- 1.5%, P = 0.042). The effect on HbA1c persisted to be significant with adjustments to age and BMI. In men, the associations between the polymorphism and glycemic control parameters were non-significantly noted. There were no differences between genotype-based groups in the other metabolic parameters in both sexes. Conclusion These results suggest that the AT2R A/C3123 polymorphism could be a polymorphic marker related to glycemic control, as presented in HbA1c, among general Japanese women.

Short-term low calorie diet intervention reduces serum advanced glycation end products in healthy overweight or obese adults.

BACKGROUND: Obesity is a metabolic and cardiovascular risk factor. A low calorie diet (LCD) is one of the treatment modalities for weight loss. Serum advanced glycation end products (AGEs) are linked to increased atherogenicity and inflammation in diseases such as diabetes and renal failure. Obesity has an inflammatory component, but interestingly there are no studies on serum AGE levels in obesity or on the effects of LCD as a therapeutic measure on these markers of glycation. AIM: We hypothesized that weight loss by caloric restriction has a beneficial effect on serum AGE levels. We investigated the prospective effects of a sole LCD intervention for weight loss on serum AGEs in a cohort of overweight and non-morbidly obese but otherwise healthy subjects. METHODS: A total of 37 Japanese subjects (30 females, 7 males, mean age 48.2 +/- 9.3 years) with a mean BMI of 28.3 +/- 3.2 participated in this study. During the intervention period of 2 months, they were placed on an LCD (Diet's; 5,023 kJ/day) with meal replacement every dinner. The following data were evaluated pre- and post-intervention: AGEs, BMI, waist circumference, blood pressure, serum glucose, cholesterol, triglycerides, HDL- and LDL- cholesterol. RESULTS AND DISCUSSION: After the intervention, BMI levels were clearly reduced by 6.3% (p < 0.001), waist circumference by 5.7% (p < 0.002) and triglycerides by 11.9 % (p < 0.002). At baseline, AGEs levels were 63 +/- 11 AU for obese subjects and 63 +/- 14 for control subjects (not significant). After intervention, AGEs were reduced by 7.21% (range 0-35%, p < 0.001). The percent change in AGEs was significantly and positively correlated with that of triglycerides (r = 0.42, p < 0.009), waist circumference (r = 0.40, p < 0.011), and BMI (r = 0.42, p < 0.007). We show for the first time that serum AGEs can be reduced by an LCD intervention on weight loss, a change that correlates with the reduction in triglycerides. This may plausibly be a reflection of a reduction in glycation/lipoxidation due to the caloric restriction and its metabolic consequences, or it may be due to the decreased intake of food containing glycotoxins, or a combination of both.

Low-calorie diet-induced reduction in serum HDL cholesterol is ameliorated in obese women with the -3826 G allele in the uncoupling protein-1 gene.

The uncoupling protein-1 (UCP1) gene is of major importance for regulation of body weight and lipid/lipoprotein metabolism. Our cross-sectional study has shown that subjects with the G/G genotype of the -3826 A/G polymorphism in the UCP-1 gene have higher levels of serum high-density lipoprotein cholesterol (HDL-C) than those with other genotypes. Low circulating HDL-C level has been regarded as a major atherosclerotic risk factor. We therefore investigated whether the -3826 A/G polymorphism affects the obesity- and lipid-related parameters during a low-calorie diet (LCD) intervention. In 32 obese women (49.9 +/- 8.4 years of age), anthropometric, physiological and biochemical characteristics were measured before and after a 2-month LCD treatment, which restricted each subject to the same energy intakes, such as 5,120 kJ/day. The -3826 A/G polymorphism was detected using a PCR-restriction fragment-length polymorphism method. There were 6 subjects with the A/A genotype, 15 with the A/G genotype and 11 with the G/G genotype. The LCD intervention decreased weight (P < 0.001) and serum HDL-C levels (P < 0.05) in all subjects. There was no difference in the levels of change in weight, nutrient intake, physiological measurements in energy expenditure, and fat oxidation between subjects with and without the G allele. In contrast, the degree of the reduction in the HDL-C levels was significantly smaller in subjects with the G allele than those without the G allele. These results suggest that the G allele at -3826 in the UCP1 gene may ameliorate the reduction in serum HDL-C levels in obese women during LCD.

The common -55 C/T polymorphism in the promoter region of the uncoupling protein 3 gene reduces prevalence of obesity and elevates serum high-density lipoprotein cholesterol levels in the general Japanese population.

Uncoupling protein 3 (UCP3) is considered to be associated with obesity, given its function in the regulation of energy and lipid metabolism. An increased body mass index (BMI) and a decreased level of high-density lipoprotein cholesterol (HDL-C) are risk factors for cardiovascular disease. The purpose of this study was to investigate whether the UCP3 promoter -55 C/T single nucleotide polymorphism (UCP3 -55 C/T SNP) was associated with obesity according to the criteria for Japanese (BMI > or = 25 kg/m2), BMI, and serum HDL-C levels in the general Japanese population. The subjects, numbering 282 and aged 65 +/- 13 years (mean +/- SD), were recruited through an annual health checkup of residents of Mima city, Tokushima, in Japan. Body mass index, blood pressure, biochemical indexes including lipid, and lipoprotein profiles were measured. The UCP3 -55 C/T SNP was determined with a fluorescence-based allele-specific DNA primer assay system. The frequency of the -55 T allele was 30.0%. Subjects with the T/T genotype had significantly higher HDL-C levels than those with the C/C genotype or the C/T genotype. Furthermore, subjects with the T/T genotype had a significantly lower BMI than those with the C/C genotype. A multivariate analysis revealed that the -55 T allele was a significant independent variable contributing to the variance in HDL-C levels and BMI. The T/T genotype was associated with a lower prevalence of obesity than the C/C and C/T genotypes, with an odds ratio of 0.358 (95% confidence interval, 0.132-0.972; P = .037). In conclusion, the UCP3 -55 C/T SNP was associated with elevated HDL-C levels and a reduced BMI, independent of modifiable factors such as lifestyle. Furthermore, this polymorphism, when expressed in its homozygous form, reduced the prevalence of obesity in Japanese.

Oxidative stress, inflammation, and atherosclerotic changes in retinal arteries in the Japanese population; results from the Mima study.

Oxidative stress and inflammation are known to play roles in the pathogenesis of vascular events. The aim of this study was to investigate the relationship between oxidative stress, inflammation, and atherosclerosis in the general population. A population-based, cross-sectional study was made of 282 people (126 men and 156 women, mean age; 65 13, mean BMI; 25.4 2.7 kg/m (2) ) recruited from the Mima study in Tokushima Prefecture. Risk factors included age, sex, body mass index (BMI), cigarette smoking, systolic and diastolic pressure, fasting blood glucose, serum lipids, and high-sensitive C-reactive protein (hs-CRP). Oxidative stress in blood samples was measured by the diacron reactive oxygen metabolites (ROMs) test. The degree of sclerotic change was determined from fundus photographs according to Scheie's classification. After adjustment for age and sex, ROM levels positively correlated with hs-CRP levels, but not with ghrelin, leptin and adiponectin levels. Furthermore, ROM and hs-CRP levels positively and individually correlated with the grade of sclerotic change in the fundus oculi independent of age in a multiple regression analysis. These results suggest that oxidative stress and chronic inflammation promote atherosclerosis in the retinal arteries in the general population.

Association of Pro12Ala polymorphism in the peroxisome proliferator-activated receptor gamma2 gene with small dense low-density lipoprotein in the general population.

The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma2 (PPARgamma2) gene has been reported to predict a lower risk for developing type 2 diabetes mellitus. However, its effect on the lipid profile has been disputable. Among low-density lipoproteins, small dense low-density lipoprotein (sdLDL) particles have been linked to a greater risk for coronary artery disease. The purpose of this study was to investigate the genetic effect of the Pro12Ala polymorphism in the PPARgamma2 gene on the presence of sdLDL in the general Japanese population. In 379 subjects (aged 54 +/- 13 years), body mass index, percentage of body fat, blood pressure, and biochemical profiles were measured. Pro12Ala polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism. The area of sdLDL subfractions (sdLDL4-7) was analyzed by high-resolution polyacrylamide gel electrophoresis. The frequency of the Ala12 allele in PPARgamma2 was 0.04. There was no difference in total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels between genotypes. However, subjects with the X/Ala genotype (Pro/Ala + Ala/Ala) had significantly higher serum triglyceride levels (P = .001) and a larger area of sdLDL4-7 (P = .002) than those with the Pro/Pro genotype. Multiple regression analysis revealed that the Ala12 allele was a significant variable contributing to the variance in the increased area of sdLDL4-7 (P = .040). In conclusion, the Pro12Ala polymorphism in the PPARgamma2 gene was positively associated with an enlarged area of sdLDL4-7. This polymorphism may play a role in the genetic predisposition to increases in sdLDL4-7.

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is associated with increased small dense low-density lipoprotein in a rural Japanese population: the Mima study.

The presence of small dense low-density lipoprotein (sdLDL) is closely associated with an increased risk of developing coronary artery disease. The Trp64Arg polymorphism of the beta(3)-adrenergic receptor (beta(3)-AR) gene is a genetic marker for obesity-related traits. However, any possible association between this polymorphism and sdLDL profiles is unclear. The objective of this study is to investigate the effects of the polymorphism of the beta(3)-AR gene on LDL particle size and sdLDL in a rural Japanese population. Among 277 subjects, body mass index, blood pressure, fasting serum insulin levels, and insulin resistance index (fasting glucose x fasting insulin/405) were determined. The polymorphism of the beta(3)-AR gene was assessed by polymerase chain reaction-restriction fragment length polymorphism using buccal samples. Low-density lipoprotein particle size and sdLDL were measured with the electrophoretic separation of lipoproteins on the LipoPrint System (Quantimetrix, Redondo Beach, CA). The frequency of the beta(3)-AR allele was 0.19. In Arg carriers (Trp/Arg or Arg/Arg), the mean value of LDL particle size was smaller than that of non-Arg carriers (Trp/Trp) (P < .05). The area percentage of sdLDL was higher in Arg carriers (P < .05) than in non-Arg carriers. A multiple regression analysis showed that the area percentage of sdLDL was correlated with the polymorphism of the beta(3)-AR gene (P < .05), independently of age, sex, body mass index, smoking, and insulin resistance index. The present findings suggest that the beta(3)-AR gene polymorphism plays a role in the genetic predisposition to increased sdLDL, independently of insulin resistance.

Lifestyle-related determinants and serum adiponectin concentrations in a general population of Japanese females.

BACKGROUND: Serum adiponectin concentration plays a role in the development of metabolic and atherosclerotic diseases. Although elucidating the determinants that affect circulating adiponectin concentrations including lifestyle factors are important, little is known about the relationships between lifestyle and adiponectin in the general Japanese female population. METHODS: A total of 311 Japanese females (mean age 54 years) with normal lifestyles and taking no medications were enrolled in a community-based cross-sectional study to investigate which lifestyle factors were associated with serum adiponectin concentrations. Adiponectin was measured with an enzyme-linked immunosorbent assay. The modified Breslow's index (a well-known comprehensive index) was used in assessing lifestyle factors. RESULTS: The group of moderate drinkers (consuming 1-3 go/day on average) had significantly higher serum adiponectin concentrations than that of nondrinkers (consuming <1 go/day) (15.0 +/- 7.2 vs. 12.0 +/- 6.5 microg/mL). Using a partial correlation analysis on serum adiponectin concentrations adjusted for age and all lifestyle factors, there were significant positive correlations with age (r = 0.197) and alcohol intake (r = 0.130) and a significant inverse correlation with body mass index (BMI) (r = -0.178). CONCLUSIONS: Among many lifestyle factors, in addition to maintaining decreased BMI levels, moderate alcohol intake habits may have a significant, independent, and positive effect on adiponectin concentrations in the general population of Japanese females, similar to that of Caucasian populations.

The angiotensin II type 2 receptor gene polymorphism and body mass index in healthy Japanese women.

BACKGROUND: Angiotensin II (AngII), through the AngII type 2 receptor (AT2-R), might exert some effect on adipocyte- and lipogenesis-related biology. The Adenine/Cytosine 3123 (A/C(3123)) polymorphism in the AT2-R gene is reportedly involved in some diseases, such as hypertension. METHODS: A total of 201 healthy Japanese women (mean age 43.2 years) were enrolled in the study to investigate the association among the AT2-R A/C(3123) polymorphism detected by polymerase chain reaction methods, body mass index (BMI) and other obesity-linked metabolic parameters (blood pressure, serum lipid/lipoprotein, plasma glucose). RESULTS: Homozygotes of the C-allele in the AT2-R A/C(3123) polymorphism were associated with small but significant increases in BMI levels. There were no differences between genotype-based groups in the obesity-linked metabolic parameters. CONCLUSION: These findings suggest that the AT2-R A/C(3123) polymorphism could be a polymorphic marker related to BMI in Japanese women.

Effects of telephone-delivered lifestyle support on the development of diabetes in participants at high risk of type 2 diabetes: J-DOIT1, a pragmatic cluster randomised trial.

OBJECTIVES: To examine the effects of telephone-delivered lifestyle coaching on preventing the development of type 2 diabetes mellitus (T2DM) in participants with impaired fasting glucose (IFG). DESIGN: Cluster randomised trial. SETTING: 40 groups from 17 healthcare divisions in Japan: companies (31), communities (6) and mixed settings (3). PARTICIPANTS: Participants aged 20-65 years with fasting plasma glucose (FPG) of 5.6-6.9 mmol/L were invited from the 17 healthcare divisions. RANDOMISATION: The groups were then randomly assigned to an intervention or a control arm by independent statisticians according to a computer-generated list. INTERVENTION: The intervention arm received a 1-year telephone-delivered intervention provided by three private lifestyle support centres (at different frequencies: low-frequency (3 times), middle-frequency (6 times) and high-frequency (10 times) support calls). The intervention and control arms both received self-help devices such as a weight scale and pedometer. OUTCOMES: Participants were followed up using data from annual health check-ups and a questionnaire regarding lifestyle. The primary outcome was the development of T2DM defined as FPG ≥ 7.0 mmol/L, the diagnosis of diabetes, or use of an antidiabetic drug, confirmed by referring to medical cards. RESULTS: Of 14,473 screened individuals, participants were enrolled in either the intervention (n = 1240) arm or control (n = 1367) arm. Overall, the HR for the development of T2DM in the intervention arm during 5.5 years was 1.00 (95% CI 0.74 to 1.34). In the subanalysis, the HR was 0.59 (95% CI 0.42 to 0.83) in the subgroup that received phone calls the most frequently, compared with the control arm. A limitation of the study includes a lack of blinding. CONCLUSIONS: High-frequency telephone-delivered lifestyle support could effectively prevent T2DM in participants with IFG in a primary healthcare setting, although low-frequency and middle-frequency phone calls did not. TRIAL REGISTRATION NUMBER: This trial has been registered with the University Hospital Medical Information Network (UMIN000000662).

The relationship between adiponectin, an adiponectin gene polymorphism, and high-density lipoprotein particle size: from the Mima study.

This study examined the association among serum adiponectin levels, a single nucleotide polymorphism (SNP) of the adiponectin gene, and the size of serum high-density lipoprotein (HDL) particles in a general population. A total of 275 subjects were examined as part of the community-based Mima study. Serum adiponectin levels were measured with an enzyme-linked immunosorbent assay. Serum small-sized HDL was measured with the electrophoretic separation of lipoproteins using the Lipoprint system. Single nucleotide polymorphism G276T (rs1501299, SNP276) of the adiponectin gene was determined with a fluorescent allele-specific DNA primer assay system. Age- and sex-adjusted correlation test revealed a significant inverse relationship between small-sized HDL and adiponectin levels (r = -0.236, P < .001). More percentages of small-sized HDL were observed in the subjects with the SNP276 G/G and G/T genotypes than in those with the T/T genotype (5.5% ± 5.0% vs 3.0% ± 2.9%, P = .016). In a multiple regression analysis, small-sized HDL was significantly and independently correlated with triglycerides levels (ß = 0.133, P = .030), adiponectin levels (ß = -0.242, P < .001), and the SNP276 G allele (ß = -0.142, P = .014). Our findings indicated that adiponectin and SNP276 of the adiponectin gene may modify the size of HDL particles.

The Association Between the Uncoupling Protein-1 Gene A-3826G Polymorphism and High-density Lipoprotein Cholesterol in A General Japanese Population: A Consideration of the Obesity Status.

BACKGROUND: Limited studies have shown inconsistent data about the association between the uncoupling protein 1 (UCP1) gene A-3826G polymorphism and high-density lipoprotein (HDL) cholesterol levels. The present study investigated the association between the A-3826G polymorphism and low HDL-cholesterolemia in non-obese and obese subjects. METHODS: Anthropometric and biochemical factors, in addition to genotyping by an allele-specific DNA assay, were measured in 294 community-dwelling Japanese subjects (male/female: 127/167, mean age: 65 years). Obesity was defined as a body mass index (BMI) ≥ 25 kg/m(2), and low HDL-cholesterolemia was defined as < 1.04 mmol/L of HDL-cholesterol. RESULTS: The subjects with the G/G genotype (n = 27) showed a significantly higher prevalence of low HDL-cholesterolemia (37%) than those with the A/A + A/G genotype (13%) in the obese group (n = 102). There was a non-significant difference in the prevalence of low HDL-cholesterolemia between subjects with the G/G genotype (n = 45, 13%) and with the A/A + A/G genotype (15%) in the non-obese group (n = 192). A multivariate-adjusted logistic regression analysis of the presence of low HDL-cholesterolemia revealed that carrying the G/G genotype was an independent and significant factor positively associated with low HDL-cholesterolemia [odds ratio (OR): 6.85, 95% confidence interval (CI): 1.65-28.49] in the obese group, while carrying the G/G genotype exhibited a non-significant but reduced OR, by one-half, for low HDL-cholesterolemia (OR: 0.51, 95% CI: 0.13-1.96) in the non-obese group. CONCLUSIONS: The obesity status could have opposing impacts on the relationship between the G/G genotype and low HDL-cholesterolemia, providing insight into the need to consider the obesity levels when studying the association between the UCP-1 gene A-3826G polymorphism and HDL-cholesterol. KEYWORDS: Obesity; Body mass index; HDL-C; Atherosclerotic risk.

Genetic polymorphisms of the renin-angiotensin system and obesity-related metabolic changes in response to low-energy diets in obese women.

OBJECTIVE: Genetic polymorphisms of the renin-angiotensin system have been implicated in cardiovascular and metabolic diseases. The purpose of this study was to investigate whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 3123C/A polymorphism of the angiotensin II type 2 receptor (AT(2)R) gene affect blood pressure and other obesity-related metabolic changes in response to low-energy diets using meal replacement shakes for weight loss. METHODS: Clinical, metabolic, and biochemical profiles were measured before and after a 2-mo intervention in 32 obese women (age 49.9 ± 8.4 [SD] y; BMI 28.4 ± 3.3 kg/m²) restricted to 1200 kcal/d (5021 kJ/d). The polymorphisms were determined with an intercalater-mediated FRET probe assay system. RESULTS: Although weight loss and nutrient intake levels did not differ among the genotypes, the reduction in body fat after weight loss was significantly less in the ACE deletion/deletion (D/D) genotype than insertion/insertion (I/I) plus I/D genotype (-2.25 ± 1.40% versus -0.80 ± 1.57%, P < 0.05). The AT2R A/A group had significantly less improved levels of systolic blood pressure (-7.23 ± 8.50 versus 2.50 ± 12.6 mmHg, P < 0.05), low-density lipoprotein-cholesterol (-0.36 ± 0.29 versus -0.09 ± 0.25 mmol/L, P < 0.05), carbohydrate (-54.4 ± 27.2 versus -31.8 ± 16.3 mg/min, P < 0.05) and fat oxidation (8.31 ± 11.86 versus 0.05 ± 9.99 mg/min, P < 0.05) than the C/C plus C/A genotypes. CONCLUSION: The present findings suggest that the homozygous form of the ACE gene may hinder the improvement of body fat and that the homozygous form of the AT2R gene may make improving systolic blood pressure and some obesity-related metabolic parameters through a dietary intervention difficult among obese women.