Japanese Health Checkup Research Articles

Longevity-associated mitochondrial DNA 5178 C/A polymorphism modulates the effects of coffee consumption on erythrocytic parameters in Japanese men: an exploratory cross-sectional analysis.

BackgroundMitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism reportedly modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia and abnormal glucose tolerance. The objective of this analysis was to investigate whether Mt5178 C/A polymorphism modifies the effects of coffee consumption on erythrocytic parameters in male Japanese health check-up examinees.MethodsA total of 436 men (mean age ± standard deviation, 54.1 ± 7.8 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, an exploratory cross-sectional analysis assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption on red blood cell counts, hematocrit and hemoglobin was conducted.ResultsFor Mt5178C genotypic men, after adjustment for age, body mass index, alcohol consumption, habitual smoking and green tea consumption, coffee consumption significantly decreased red blood cell counts (P for trend = 0.022) and hemoglobin (P for trend = 0.035). The risk of anemia, defined as hemoglobin of <14 g/dL, after the aforementioned adjustment, appeared to depend on coffee consumption (P for trend = 0.078), and the adjusted odds ratio for anemia was significantly higher in men who consumed ≥4 cups of coffee per day than in those who consumed <1 cup per day (odds ratio = 3.771, 95% confidence interval: 1.088 to 13.06, P = 0.036). For Mt5178A genotypic men, coffee consumption possibly reduced the risk of anemia (P for trend = 0.049). However, after the aforementioned adjustment, the statistical significance disappeared (P for trend = 0.137).ConclusionsThis exploratory cross-sectional analysis suggests that Mt5178 C/A polymorphism modulates the effects of coffee consumption on erythrocytic parameters and the risk of anemia in male Japanese health check-up examinees.

Significance of estimated glomerular filtration rate in predicting brain or heart attacks in obese and non-obese populations.

The Japanese Specific Health Checkup mainly focuses on metabolic syndrome for preventing cardiovascular events. Subjects are stratified by measuring waist circumference, body mass index, blood pressure, triglycerides, and fasting plasma glucose. However, estimated glomerular filtration rate (eGFR) is not considered essential. A longitudinal cohort study assessed the association of eGFR with new-onset brain or heart attacks in a large Japanese nationwide Specific Health Checkup database. A total of 109,349 Japanese subjects (mean age 63.2 years, 39.5 % men) were examined for the events 2 years later. The odds ratios were calculated for new events in the total and subgroup populations divided by BMI < or ≥25 kg/m(2), obese and non-obese, respectively. Obese subjects were more often male and had proteinuria (dipstick test ≥1+), lower eGFR, and higher systolic and diastolic BP, fasting plasma glucose, hemoglobin A1c, and triglycerides (TG). Rates of new-onset brain or heart attacks were 3.1 and 4.0 % in the groups of non-obese and obese subjects, respectively. In the total population, eGFR as well as higher BMI (≥25 kg/m(2)), higher BP (high-normal hypertension or greater), higher TG (≥150 mg/dl), and proteinuria were significant risk factors for developing brain or heart attacks. The eGFR was significant in non-obese subjects, but not in the obese. As the ultimate aim of 'Specific Health Checkup' is to prevent cardiovascular events, our study suggests that eGFR should be evaluated in non-obese subjects.

NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modifies effects of cigarette smoking on risk of elevated levels of serum liver enzyme in male Japanese health check-up examinees: a cross-sectional study.

BackgroundNADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism reportedly influences the effects of cigarette smoking on respiratory function, risk of dyslipidemia, serum non-high-density lipoprotein cholesterol levels, hematological parameters and intraocular pressure. The objective of this study was to investigate whether ND2-237 Leu/Met polymorphism modifies the effects of cigarette smoking on serum liver enzyme levels in male Japanese health check-up examinees.MethodsA total of 421 male subjects (mean age ± SD, 54.1 ± 7.7 years) were selected from among individuals visiting the hospital for regular medical check-ups. After ND2-237 Leu/Met genotyping, a cross-sectional study assessing the combined effects of ND2-237 Leu/Met polymorphism and cigarette smoking on serum aspartate aminotransferase levels, serum alanine aminotransferase (ALT) levels and serum gamma-glutamyltransferase (GGT) levels was then conducted.ResultsNo statistically significant differences in serum liver enzyme levels among the three smoking status groups (never- or ex-smokers, 1–20 cigarettes smoked per day and >20 cigarettes smoked per day) by ND2-237 Leu/Met genotype were observed. However, for men with ND2-237Met, cigarette smoking significantly increased the risk of elevated levels of serum ALT (>30 U/L) or serum GGT (≥60 U/L or >51 U/L) (P for trend = 0.031, P for trend = 0.007 and P for trend = 0.004, respectively). After adjustment for age, body mass index, alcohol consumption, coffee consumption, antihypertensive treatment and antidiabetic treatment, a significant association between cigarette smoking and risk of elevated levels of serum ALT (>30 U/L) or serum GGT (≥60 U/L or >51 U/L) was also observed (P for trend = 0.032, P for trend = 0.019 and P for trend = 0.009, respectively). Surprisingly, for men with ND2-237Leu, cigarette smoking significantly decreased the risk of elevated levels of serum ALT (>30 U/L or ≥25 U/L) (P for trend = 0.026 and P for trend = 0.003, respectively).ConclusionsCigarette smoking appears to increase the risk of elevated levels of serum ALT or serum GGT in ND2-237Met genotypic men, but to decrease the risk of elevated levels of serum ALT in ND2-237Leu genotypic men.

Unexpected combined effects of NADH dehydrogenase subunit-2 237 Leu/Met polymorphism and green tea consumption on renal function in male Japanese health check-up examinees: a cross-sectional study

BackgroundNADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with longevity in Japanese. A previous study has shown that ND2-237 Leu/Met polymorphism modulates the effects of green tea consumption on risk of hypertension. For men with ND2-237Leu, habitual green tea consumption may reduce the risk of hypertension. Moreover, there is a combined effect of ND2-237 Leu/Met polymorphism and alcohol consumption on risk of mildly decreased estimated glomerular filtration rate (eGFR) (<90 ml/min/1.73 m2). Several beneficial effects of green tea on the kidney have been reported. The objective of this study was to investigate whether ND2-237 Leu/Met polymorphism modifies the effects of green tea consumption on risk of mildly decreased eGFR in male Japanese health check-up examinees.ResultsFor ND2-237Leu genotypic men, after adjustment for confounding factors, green tea consumption may increase the risk of mildly decreased eGFR (P for trend = 0.016). The adjusted odds ratio (OR) for mildly decreased eGFR was significantly higher in subjects with ND2-237Leu who consume ≥6 cups of green tea per day than those who consume ≤1 cup of green tea per day (adjusted OR = 5.647, 95% confidence interval: 1.528-20.88, P = 0.009). On the other hand, for ND2-237Met genotypic men, green tea consumption does not appear to determine the risk of mildly decreased eGFR.ConclusionThe present results suggest that ND2-237 Leu/Met polymorphism unexpectedly modifies the effects of green tea consumption on eGFR and the risk of mildly decreased eGFR in male Japanese subjects.

Combined effect of mitochondrial DNA 5178 C/A polymorphism and alcohol consumption on estimated glomerular filtration rate in male Japanese health check-up examinees: a cross-sectional study

BackgroundPrevention of chronic kidney disease (CKD) is a major public health issue. Although several studies have been performed on the association between alcohol consumption and CKD or renal function, it remains controversial. Numerous genetic polymorphisms have been reported to be associated with CKD and kidney function. Mitochondrial DNA cytosine/adenine (Mt5178 C/A) polymorphism is associated with longevity in Japanese. This polymorphism modifies the effects of alcohol consumption on blood pressure, risk of hypertension, serum triglyceride levels, risk of hyper-LDL cholesterolemia and serum uric acid levels. The objective of this study was to investigate whether Mt5178 C/A polymorphism modifies the effects of alcohol consumption on renal function in male Japanese health check-up examinees.MethodsA total of 394 male subjects aged 29–76 years were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the combined effects of Mt5178 C/A polymorphism and habitual drinking on the risk of mildly decreased estimated glomerular filtration rate (eGFR) (<90 ml/min/1.73 m2) was conducted.ResultsFor Mt5178A genotypic men, habitual drinking may increase eGFR (P for trend = 0.003) or reduce the risk of mildly decreased eGFR (P for trend = 0.003). Daily drinkers had a significantly higher eGFR than non-drinkers (P = 0.005). The crude odds ratio for decreased eGFR was significantly lower in daily drinkers than in non-drinkers (odds ratio = 0.092, 95% confidence interval: 0.012-0.727, P = 0.024). On the other hand, for Mt5178C genotypic men, habitual drinking does not appear to affect eGFR.ConclusionThe present results suggest a joint effect of Mt5178 C/A polymorphism and alcohol consumption on eGFR and the risk of mildly decreased eGFR in male Japanese subjects.

Trend of Incidence in Positive Cervical Smears from 2002-2010 in Ningen Dock, a Special Japanese Health Check-up System

Trend of Incidence in Positive Cervical Smears from 2002-2010 in Ningen Dock, a Special Japanese Health Check-up System

Sirtuin 1 gene polymorphisms are associated with body fat and blood pressure in Japanese

Sirtuin 1 (SIRT1) is a longevity gene that protects cells against oxidative and genotoxic stress. This study aimed to investigate the associations of SIRT1 gene single nucleotide polymorphisms (SNPs), rs7895833, rs7069102, and rs2273773, with various laboratory data in 1279 Japanese health checkup examinees. The genotyping was performed using a polymerase chain reaction (PCR) with confronting 2-pair primers (CTPP) assay. Concerning rs7895833 (A allele frequency: 0.290), body fat ratio and body mass index were high in the AA carriers of male subjects, and diastolic blood pressure was high in the AA carriers of female subjects. Concerning rs7069102 (G allele frequency: 0.181), body fat ratio and systolic blood pressure were high in the GG carriers of male subjects. Concerning rs2273773 (C allele frequency: 0.323), fasting glucose and body fat ratio were high in the TT carriers of male subjects, and systolic and diastolic blood pressures were high in the CC carriers of male subjects. Thus, the A allele of rs7895833, G allele of rs7069102, and T allele of rs2273773 carried a high risk for obesity in men. Furthermore, the A allele of rs7895833 in women, and the G allele of rs7069102 and C allele of rs2273773 in men, carried a high risk for hypertension. The T allele of rs2273773 in men carried a high risk for hyperglycemia. In conclusion, these SIRT1 gene polymorphisms are associated with high body fat and blood pressure in Japanese, especially in men. The allele frequencies of rs7895833 and rs7069102, which are different from Caucasians, might explain why Japanese show less marked obesity compared with Caucasians.

SLC22A12 W258X frequency according to serum uric acid level among Japanese health checkup examinees.

Although the SLC22A12 (uric acid transporter 1) 258X allele is known to cause hypouricemia, the genotype frequency according to the serum uric acid (SUA) level has not been reported. This study investigated the SLC22A12 258WX frequency according to SUA levels among Japanese health-checkup examinees. In addition, the changes were reported in SUA levels during five years for individuals with 258WX. Subjects were 746 Japanese aged 39-86 years in 2003. Their SUA records were linked during the five years from 2003 to 2007. SLC22A12 W258X was genotyped using a polymerase chain reaction with confronting two-pair primers. The 258X allele comprised 1.9% (95% CI, 1.3-2.8%) of all the subjects. Among those with SUA <3.0 mg/dL, 258WX was more common in males (66.7%, 95% CI, 22.2-95.7%) than in females (39.3%, 95% CI, 21.5-59.4%). Among subjects with a SUA of 3.0-4.9 mg/dL, those with 258WX totaled 10.7% (95% CI, 4.0-21.9%) and 2.6% (95% CI, 1.1-5.0%), respectively. There were no subjects with 258WX among those with a SUA of 5.0 mg/dL or more. During the five years from 2003 to 2007, the changes in SUA among 23 individuals with 258WX were found to be similar to those among 258WW subjects (n=536). This study indicated that SLC22A12 258WX was more common among those with a lower serum uric acid concentration. The observed SUA level changes in individuals with 258WX suggested that lifestyle factors could influence the levels of those with 258WX.

Participation in health check-ups and mortality using propensity score matched cohort analyses

Objective All Japanese aged ≥ 40 years are eligible for free annual health check-ups including blood pressure and cholesterol measurements. It is well known that health check-up screenees are more likely to have healthy lifestyles and better health conditions than non-screenees. Therefore, controlling these factors is required to investigate whether screenees have a lower mortality risk than non-screenees independent of their lifestyles or health conditions. Methods We followed 48,775 Japanese National Health Insurance beneficiaries aged 40–79 years since 1994 for 11 years. We used Cox proportional hazard models adjusted for possible confounding factors. We also performed propensity for use of the health check-up matched cohort analyses. Results Compared to non-screenees, multiple-adjusted hazard ratios (95% confidence intervals) for all-cause and cardiovascular disease mortality among screenees were 0.74 (0.62–0.88) and 0.65 (0.44–0.95) for men and 0.69 (0.52–0.91) and 0.61 (0.36–1.04) for women, respectively. These relations were also observed when we used propensity matched cohort analyses. Conclusion This is the first study to show that mortality rates are lower among screenees than non-screenees in Japanese health check-ups when propensity matched cohort analyses were used for adjusting confounding factors. Further prospective studies, including randomized controlled trials, are required to confirm whether screening lowers mortality.

Association between Decreased Kidney Function and Endotoxin Receptor CD14 C-159T Polymorphism among Japanese Health Check-up Examinees

Background. A recently identified promoter polymorphism of the endotoxin receptor (CD14 C-159T) was shown to be associated with atherosclerotic diseases such as myocardial infarction. This study was conducted to determine whether this polymorphism is associated with decreased kidney function. Methods. A total of 281 male and 522 female health check-up examinees, aged 39–88 years, were genotyped for CD14 C-159T. The glomerular filtration rate (GFR) was estimated by the Modification of Diet in Renal Disease (MDRD) Study equation. Estimated GFR (eGFR) and the proportion of subjects with mildly decreased eGFR (eGFR under 90 mL/min/1.73 m2) were compared among the genotypes. Results. Subjects carrying the T allele showed decreased age- and sex-adjusted eGFR compared with those with CC genotype (101±22 vs. 105±23 mL/min/1.73 m2; mean±SD, p = 0.012). The proportion of subjects with mildly decreased eGFR was higher in T allele carriers (34.2% for TT+CT and 26.3% for CC genotype, p = 0.041), but not statistically significant when adjusted for age and sex (odds ratio [OR] 1.41, 95% CI 0.97–2.05, p = 0.076). In subjects under 65 years, T allele carriers had a significantly increased risk for mildly decreased eGFR (27.1% for TT+CT and 18.0% for CC; age- and sex-adjusted OR 1.82, 95% CI 1.06–3.12, p = 0.030). Conclusion. CD14-159T allele was associated with decreased eGFR compared with CC genotype, and with a higher prevalence of mildly decreased eGFR in younger subjects under 65.

Grb2-associated binder 1 polymorphism was associated with the risk of Helicobactor pylori infection and gastric atrophy

Various single nucleotide polymorphisms (SNPs) have explained the association between Helicobacter pylori (H. pylori) and gastric atrophy and cancer. This study investigated the associations of Grb2 associated binder 1 (Gab1) polymorphism and the combination of PTPN11 gene encoding src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP2) and Gab1 gene with gastric cancer and gastric atrophy among H. pylori seropositive subjects. A single nucleotide polymorphism at intron 2 of Gab1 (JST164345) was examined for 454 Japanese health checkup examinees (126 males and 328 females) aged 35 to 85 without a history of gastric cancer and 202 gastric cancer patients (134 males and 68 females) aged 33 to 94 with pathologically confirmed diagnosis of gastric adenocarcinoma. The decreased OR of the Gab1 A/A for H. pylori seropositivity was 0.25 (95% confidence interval (CI): 0.08-0.71). Among seropositive healthy controls, the OR of the Gab1 G/A+A/A for gastric atrophy was significant (OR=1.95, 95% CI: 1.12 -3.40). Seropositive individuals with PTPN11 G/G and Gab1 G/A+A/A demonstrated the highest risk of gastric atrophy with significance (OR=3.49, 95% CI: 1.54-7.90) relative to PTPN11 G/A+A/A and Gab1 G/G, the lowest risk combination, as a reference. However, the gene-gene interaction between PTPN11 and Gab1 was not observed (OR=1.39, 95% CI: 0.41-4.66). Compared to gastric cancer case, the Gab1 did not influence the step of atrophy/metaplasia-gastric cancer sequence. This study represents that the Gab1 polymorphism was associated with the low risk of H. pylori infection and the high risk of gastric atrophy among seropositive healthy controls, and that seropositive individuals with PTPN11 G/G and Gab1 G/A+G/G were associated with the greatest risk of gastric atrophy. These findings require confirmation in much larger studies.

Inducible nitric oxide synthase polymorphism is associated with the increased risk of differentiated gastric cancer in a Japanese population

To examine the association of inducible nitric oxide synthase (iNOS) C150T polymorphism with gastric cancer, as well as with gastric atrophy and H pylori seropositivity. A single nucleotide polymorphism of iNOS C150T was examined for 454 Japanese health checkup examinees (126 males and 328 females) aged 35 to 85 years without a history of cancer and 202 gastric cancer patients (134 males and 68 females) aged 33 to 94 years with pathologically confirmed diagnosis of gastric adenocarcinoma. The iNOS C150T polymorphism was not associated with gastric atrophy or with H pylori seropositivity. The odds ratio (OR) of the C/T + T/T for gastric cancer was increased without statistical significance (OR = 1.19, 95% confidence interval (CI): 0.68-2.08). In the differentiated subgroup (n = 113), however, the OR of the C/T genotype for gastric cancer was significant (OR = 2.02, 95% CI: 1.04-3.92) relative to the C/C genotype. In addition, considering the location of gastric cancer (n = 105), there were significant differences between the controls and non-cardia group with the OR of 2.13 (95% CI: 1.08-4.18) for C/T and 1.94 (95% CI: 1.00-3.78) for C/T + T/T. The iNOS C150T polymorphism is associated with the risk of H pylori-related gastric cancer in a Japanese population. This polymorphism may play an important role in increasing the risk of gastric cancer in Asian countires with the highest rates of gastric cancer.

Duplex polymerase chain reaction with confronting two-pair primers (PCR-CTPP) for genotyping alcohol dehydrogenase beta subunit (ADH2) and aldehyde dehydrogenase 2 (ALDH2).

Alcohol dehydrogenase beta subunit (ADH2) Arg47His and aldehyde dehydrogenase 2 (ALDH2) Glu487Lys were genotyped by a duplex polymerase chain reaction (PCR) with confronting two-pair primers (PCR-CTPP), which allows DNA amplification with one-tube PCR including eight primers, and subsequent electrophoresis. Several PCR conditions were tested to establish the optimal conditions for distinguishing the allele-specific bands for the two polymorphisms. Under the optimal PCR conditions, 454 Japanese health check-up examinees were genotyped. The allele-specific bands were successfully amplified under the optimal conditions of the duplex PCR-CTPP. The genotype distributions were within the Hardy-Weinberg equilibrium. The bands produced by the duplex PCR-CTPP genotyping were clearer than those produced by PCR-CTPP, conducted solely for ADH2. ADH2 Arg47His and ALDH2 Glu487Lys were successfully genotyped by this newly developed duplex PCR-CTPP, an inexpensive and time-saving genotyping tool, which will be useful in epidemiological studies on alcoholism, as well as risk estimation of alcohol-related diseases.

Helicobacter pylori seropositivity and the myeloperoxidase G-463A polymorphism in combination with interleukin-1B C-31T in Japanese health checkup examinees.

Genetic susceptibility appears to play an important role in Helicobacter pylori (HP) infection. The present study was conducted to re-examine the reported association between the myeloperoxidase (MPO) G-463A polymorphism and HP seropositivity in different subjects and to investigate interactions with smoking behavior and the interleukin-1B (IL-1B) C-31T polymorphism. The subjects were 468 health checkup examinees in Nagoya, who consented to anonymous genotyping of residual blood samples. Genotyping was conducted by PCR-RFLP for MPO G-463A and PCR-CTPP for IL-1B C-31T. Among the successfully genotyped 437 participants without a cancer history, the HP seropositive rate was 56.2% for -463GG (n = 354), 49.4% for -463GA (n = 77) and 83.3% for -463AA (n = 6). The gender-age-adjusted odds ratio (aOR) for GA/AA relative to GG was 0.86 (95% confidence interval, 0.32-1.34) among males, 0.84 (0.47-1.49) among females, 0.83 (0.22-3.05) among current smokers and 0.87 (0.50-1.51) among never smokers. Analysis by IL-1B C-31T genotype revealed a significantly reduced OR of 0.41 (0.18-0.93) among the participants with IL-1B -31CT. The OR for IL-1B -31TT relative to -31CC/CT was 1.59 (1.00-2.55) among those with MPO -463GG and 3.36 (1.16-9.77) with MPO -463GA/AA. None of the gene-environment or gene-gene interactions proved to be statistically significant. The association between MPO G-463A and HP seropositivity was not reproduced in this study. The effect of IL-1B -31TT was more prominent among individuals with the low expression MPO -463A allele, but it remains to be confirmed for other datasets.