Background: Although beneficial associations have been reported between moderate alcohol intake and the serum lipid profile, it is unclear whether polymorphisms in alcohol-metabolizing enzymes can ...modify these associations. Here, we assessed the effects of ADH1B His48Arg (rs1229984), ALDH2 Glu504Lys (rs671), and their combination on these associations. Furthermore, we examined if the findings for ALDH2 could be replicated. Methods: We categorized 889 male participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study into two groups based on presence or absence of minor allele(s) or four groups based on genotype combinations. We performed regression analyses of serum lipid concentrations on alcohol intake, with multivariable adjustment. The replication study was conducted among 2,562 men in the Shizuoka part of the J-MICC Study. Results: The ALDH2 Glu/Lys or Lys/Lys groups showed significant decreases in serum low-density lipoprotein (LDL) cholesterol with increasing alcohol consumption; the coefficient per intake increase of 10 g/day was −2.49 mg/dL (95% confidence interval CI, −3.85 to −1.13), and a significant interaction with the polymorphism was confirmed (P for interaction = 0.006). This inverse correlation was more evident among the ADH1B His/His + ALDH2 Glu/Lys or Lys/Lys groups (−3.24 mg/dL, 95% CI, −5.03 to −1.45). Serum triglycerides were positively associated with alcohol consumption in the ADH1B His/His group (P for interaction = 0.020). The stronger association between serum LDL cholesterol and alcohol consumption in the ALDH2 Glu/Lys or Lys/Lys groups was replicated. Conclusions: The ALDH2 Glu504Lys polymorphism can modify the association between alcohol intake and serum LDL cholesterol in Japanese men.
Full text
Available for:
FFLJ, NUK, ODKLJ, UL, UM, UPUK
Background: Type 2 diabetes mellitus (T2DM) in obese has been considered a risk factor for male infertility. Garcinia mangostana pericarp extract (GMPE) is known to have anti-hyperglycemic, ...anti-diabetic, and anti-inflammatory effects. This study aimed to evaluate the effect of GMPE therapy on reproductive function in obese T2DM rats by examining testosterone level, testicular histopathological features, and hs-CRP level.Methods: Thirty-six male Wistar rats, aged 2-3 months, were randomly divided into 6 groups and treated with a standard diet (NC), high-fat diet (HFD) with GMPE 200 mg/kgBW (obese GMPE control/OGC200), HFD with 45 mg/kgBW STZ-NA (obese-diabetic control/ODC), obese-diabetic rats with GMPE 100 (DG100); 200 (DG200); and 400 mg/kgBW (DG400). STZ-NA was administered after 8 weeks of HFD treatment and followed by GMPE for 8 weeks after T2DM was confirmed. The level of hs-CRP and testosterone were measured in the serum using an enzyme-linked immunosorbent assay. Testicular histopathological examination was measured after 8 weeks of treatment by using Modified Jonhson Score (MJS) with HE staining.Results: ODC rats significantly showed increased hs-CRP level compared to NC (8.76±0.27 vs 0.30±0.07 ng/mL, P<0.001) and reduced testosterone level and MJS compared to NC (73.69±2.22 vs170.14±1.34 ng/dL, 4.57±0.93 vs 9.87±0.16 MJS, respectively, P<0.001). Testosterone and hs-CRP levels showed a negative and significant correlation (r=-0.974 and P<0.001). On the treatment group, GMPE significantly reduced hs-CRP and increased testosterone levels in a dose-dependent manner.Conclusion: GMPE effectively protects reproductive function in obese DM rats by increasing testosterone levels and advanced spermatogenesis, as well as decreasing hs-CRP level.
PURPOSEAlthough several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication ...studies have produced inconsistent results.
METHODSWe conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study.
RESULTSWe found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples.
CONCLUSIONSWe identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.
Atherosclerosis is caused by an inflammatory process in the endothelium due to an imbalance between oxidant and antioxidant agents that often occurs in Diabetes mellitus (DM) patients. Antioxidants ...that function to neutralize superoxide can be used to prevent atherosclerosis in DM. Piper crocatum leaves shows an unknown antioxidant effect on the atherosclerosis process.The aim of this study is to determine the effect Piper crocatum leaves extract on blood MDA levels and the severity of atherosclerosis in diabetic rats. 30 Sprague Dawley rats were randomly divided into 6 groups, namely, HC (nondiabetic), NC (diabetic-no therapy), PC (metformin 45 mg/kg), PC200, PC300, PC400 (Piper crocatum leaves extract 200/300/ 400 mg/kg/day). Termination, blood sampling, and histopathological analysis were performed after 14 days of treatment. MDA was measured using the TBARS method, and read on a 532 nm wavelength UV-vis spectrophotometer. The severity of atherosclerosis of the rat carotid artery was observed from tissue stained with Haematoxylin Eosin staining at 400x microscope magnification. The mean blood MDA levels in the PC200, PC300, PC400 groups were 1.24 ± 0.26, 0.85 ± 0.35, 0.10 and ± 0.02, respectively, and a decrease in MDA levels was found in the PC200, PC300, and PC400 compared to group NC. The study showed a decrease in the severity of atherosclerosis in groups PC200, PC300, PC400 compared to groups NC. Piper crocatum leaves extract had an effect on decreasing MDA levels and severity of atherosclerosis in diabetic rats.
An increased risk of total death owing to human T-lymphotropic virus type-I (HTLV-I) infection has been reported. However, its etiology and protective factors are unclear. Various studies reported ...fluctuations in immune-inflammatory status among HTLV-I carriers. We conducted a matched cohort study among the general population in an HTLV-I-endemic region of Japan to investigate the interaction between inflammatory gene polymorphisms and HTLV-I infection for total death, incidence of cancer, and atherosclerosis-related diseases.
We selected 2180 sub-cohort subjects aged 35–69 years from the cohort population, after matching for age, sex, and region with HTLV-I seropositives. They were followed up for a maximum of 10 years. Inflammatory gene polymorphisms were selected from TNF-α, IL-10, and NF-κB1. A Cox proportional hazard model was used to estimate the hazard ratio (HR) and the interaction between gene polymorphisms and HTLV-I for risk of total death and incidence of cancer and atherosclerosis-related diseases.
HTLV-I seropositivity rate was 6.4% in the cohort population. The interaction between TNF-α 1031T/C and HTLV-I for atherosclerosis-related disease incidence was statistically significant (p = 0.020). No significant interaction was observed between IL-10 819T/C or NF-κB1 94ATTG ins/del and HTLV-I. An increased HR for total death was observed in the Amami island region, after adjustment of various factors with gene polymorphisms (HR 3.03; 95% confidence interval, 1.18–7.77).
The present study found the interaction between TNF-α 1031T/C and HTLV-I to be a risk factor for atherosclerosis-related disease. Further follow-up is warranted to investigate protective factors against developing diseases among susceptible HTLV-I carriers.
•We observed death and incidence risk with HTLV-I and SNPs in a matched cohort study.•An increased risk for total death with HTLV-I was observed in the island region.•Inflammatory SNP interacted with HTLV-I for atherosclerosis-related disease risk.
Full text
Available for:
FFLJ, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, ODKLJ, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aim: Observational studies have reported that elevated homocysteine (Hcy) levels are associated with the risk of cardiovascular disease (CVD). However, interventions that lower Hcy do not provide a ...corresponding risk reduction. Therefore, the causal role of Hcy in CVD remains unclear. This 5-year prospective study investigated the associations of Hcy levels, folate intake, and host factors with arterial stiffness among the general Japanese population. Methods: We prospectively recruited 658 participants (40–69 years old) from the general population during regular health checkup examinations. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI) at baseline and the 5-year follow-up. Folate intake was estimated using a structured questionnaire. Genotyping was used to evaluate the MTHFR C677T and MS A2756G gene polymorphisms. Ultrafast liquid chromatography was used to measure total plasma Hcy levels. Association between these variables and CAVI values was evaluated using general linear regression and logistic regression models that were adjusted for atherosclerosis-related factors. Results: Men had higher Hcy levels and CAVI values and lower folate intake than women (all, p＜0.001). At baseline, Hcy, folate intake, and the two genotypes were not associated with CAVI values for both sexes. Among men, Hcy levels were positively associated with CAVI values at the 5-year follow-up (p=0.033). Folate intake and the two genotypes were not associated with the 5-year CAVI values. Conclusion: Plasma Hcy may be involved in arterial stiffness progression, as monitored using CAVI, among men.
Banana (Musa paradisiaca L.) peel, locally name pisang raja, contains a high concentration of pectin which is used as antidiarrheal to absorb irritants and increase stool consistency. However, it’s ...use to increase the stool consistency has not been studied, yet. The study aimed to investigate the effect banana peel extract (BPE) administration on stool consistency of diarrheal rat model. It was an experimental study with a post-test only control group design. Thirty male Wistar rats were induced diarrhea with castor oil and then randomized into five groups. Group I as positive control group was given attapulgite at dose of 124 mg/kg BW. Group II as negative control was given 0.5 mL of 1% tween 80. Group III, IV and V as treatment group were give BPE at different doses of 100, 200 and 400 mg/kg BW, respectively.T he stool consistency was measured every hour for 4 h by weighing fresh and dry stool weight and then the water content was calculated. Data analysis was conducted using one-way ANOVA and LSD post hoc test. Significantly different in stool consistency between Group III, IV, and V compared to Group II (p<0.05) and between groups Group III and IV compare to Group I (p<0.05) were observed. However, there was no significantly different between group V compared to Group I (p=0.149).In conclusion, BPE can increase the stool consistency of castor oil-induced diarrhea rats. The BPE at the dose of 400 mg/kg BW has similar effect to attapulgite.
Interactions between dietary patterns and 2 β-adrenergic receptor (ADRβ) gene polymorphisms (ADRβ2 Gln27Glu and ADRβ3 Trp64Arg) were examined with regard to the effects on serum triglyceride levels. ...The cross-sectional study comprised 1720 men and women (aged 35-69 years) enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Genotyping was conducted using a multiplex polymerase chain reaction-based invader assay. We used 46 items from a validated short food frequency questionnaire and examined major dietary patterns by factor analysis. We identified four dietary patterns: healthy, Western, seafood and bread patterns. There was no significant association between any dietary pattern and serum triglyceride levels. After a separate genotype-based analysis, significant interactions between ADRβ3 Trp64Arg genotype and the bread pattern (p for interaction = 0.01) were associated with serum triglyceride levels; specifically, after adjusting for confounding factors, Arg allele carriers with the bread pattern had lower serum triglycerides (p for trend = 0.01). However, the Trp/Trp homozygous subjects with the bread pattern showed no association with serum triglycerides (p for trend = 0.55). Interactions between other dietary patterns and ADRβ polymorphisms were not significant for serum triglyceride levels. Our findings suggest that ADRβ3 polymorphism modifies the effects of the bread pattern on triglyceride levels.
Aim: Observational studies have reported that elevated homocysteine (Hcy) levels are associated with the risk of cardiovascular disease (CVD). However, interventions that lower Hcy do not provide a ...corresponding risk reduction. Therefore, the causal role of Hcy in CVD remains unclear. This 5-year prospective study investigated the associations of Hcy levels, folate intake, and host factors with arterial stiffness among the general Japanese population. Methods: We prospectively recruited 658 participants (40-69 years old) from the general population during regular health checkup examinations. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI) at baseline and the 5-year follow-up. Folate intake was estimated using a structured questionnaire. Genotyping was used to evaluate the MTHFR C677T and MS A2756G gene polymorphisms. Ultrafast liquid chromatography was used to measure total plasma Hcy levels. Association between these variables and CAVI values was evaluated using general linear regression and logistic regression models that were adjusted for atherosclerosis-related factors. Results: Men had higher Hcy levels and CAVI values and lower folate intake than women (all, p<0.001). At baseline, Hcy, folate intake, and the two genotypes were not associated with CAVI values for both sexes. Among men, Hcy levels were positively associated with CAVI values at the 5-year follow-up (p=0.033). Folate intake and the two genotypes were not associated with the 5-year CAVI values. Conclusion: Plasma Hcy may be involved in arterial stiffness progression, as monitored using CAVI, among men.
PDF
