Association of obesity and diabetes with serum prostate-specific antigen levels in Japanese males.

Patients with diabetes have been reported to be at an increased risk for cancers of the pancreas, liver, and colon; however, recent studies have suggested that men with diabetes are at a decreased risk for prostate cancer. Previous studies have found that obese men have lower serum prostate-specific antigen (PSA) concentrations than do non-obese men. Further understanding of how obesity and diabetes affect the PSA concentration may improve our ability to detect clinically relevant prostate tumors. This study examined the relationships among serum PSA level, obesity, and diabetes in apparently healthy Japanese males. We analyzed the baseline data from 2,172 Japanese males (age, 56.8 +/- 6.1 years [mean +/- SD]) who participated in the Japan Multi-Institutional Collaborative Cohort Study. Diabetes was defined as the presence of both a hemoglobin A1c (JDS) of > or = 6.1% and a fasting plasma glucose level of > or = 126 mg/dL, or a positive medical history. After adjusting for age, the PSA levels were elevated among males with a higher normal BMI (ranging from 23.0 to 24.9) and lowered among men with a BMI of > or = 25.0. In the stratified analysis, these significant differences in BMI categories were absent among diabetics. The mean PSA levels were significantly lower in diabetics than in non-diabetics among subjects aged 60 and over. Our findings suggest that the pre-overweight men had increased PSA levels, and the diabetes was associated with a reduction of PSA levels in elderly.

Profile of participants and genotype distributions of 108 polymorphisms in a cross-sectional study of associations of genotypes with lifestyle and clinical factors: a project in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.

BACKGROUND: Most diseases are thought to arise from interactions between environmental factors and the host genotype. To detect gene-environment interactions in the development of lifestyle-related diseases, and especially cancer, the Japan Multi-institutional Collaborative Cohort (J-MICC) Study was launched in 2005. METHODS: We initiated a cross-sectional study to examine associations of genotypes with lifestyle and clinical factors, as assessed by questionnaires and medical examinations. The 4519 subjects were selected from among participants in the J-MICC Study in 10 areas throughout Japan. In total, 108 polymorphisms were chosen and genotyped using the Invader assay. RESULTS: The study group comprised 2124 men and 2395 women with a mean age of 55.8 ± 8.9 years (range, 35-69 years) at baseline. Among the 108 polymorphisms examined, 4 were not polymorphic in our study population. Among the remaining 104 polymorphisms, most variations were common (minor allele frequency ≥0.05 for 96 polymorphisms). The allele frequencies in this population were comparable with those in the HapMap-JPT data set for 45 Japanese from Tokyo. Only 5 of 88 polymorphisms showed allele-frequency differences greater than 0.1. Of the 108 polymorphisms, 32 showed a highly significant difference in minor allele frequency among the study areas (P < 0.001). CONCLUSIONS: This comprehensive data collection on lifestyle and clinical factors will be useful for elucidating gene-environment interactions. In addition, it is likely to be an informative reference tool, as free access to genotype data for a large Japanese population is not readily available.

Baseline data of Shizuoka area in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study).

The Japan Multi-Institutional Collaborative Cohort (J-MICC) Study launched in 2005 by ten research groups throughout Japan aimed to examine gene-environment interactions in lifestyle-related diseases, especially cancers. This paper describes one component of the J-MICC Study, named Shizuoka Study, in which visitors aged 35 to 69 years to the Seirei Preventive Health Care Center in Hamamatsu were enrolled. Among 13,740 visitors matching eligibility criteria, 5,040 persons (36.7%) were enrolled from January 2006 to December 2007. Their lifestyle, disease history, and family history were surveyed using a self-administrated questionnaire. Blood and urine were collected from the participants. By the end of December 2008, 8 withdrawers and 1 ineligible participant had been removed, leaving 5,031 participants (3,419 males and 1,612 females) as the baseline dataset. Current smokers were 23.3% among males, and 4.4% among females, and those who drank once or more per month were 76.9% and 38.6%, respectively. Those with a cancer history were 3.0% for males and 3.8% for females. Measurements out of a normal range in males and females were 11.3% and 4.0% for diastolic blood pressure > or = 90 mmHg, 11.0% and 7.6% for systolic blood pressure > or = 140 mmHg, 5.9% and 1.7% for fasting blood glucose > or = 126 mg/dl, respectively. Collected information and specimens will be cooperatively used to examine the associations of biomarkers with lifestyle, genotypes, and their combinations, as well as for a part of the J-MICC Study.

KLOTHO gene polymorphisms G-395A and C1818T are associated with lipid and glucose metabolism, bone mineral density and systolic blood pressure in Japanese healthy subjects.

BACKGROUND: We investigated the association of KLOTHO gene single nucleotide polymorphisms (SNPs) with various laboratory data in 476 Japanese healthy subjects. METHODS: The genotyping of G-395A in the promoter region and C1818T in exon 4 was performed using PCR with confronting 2-pair primers assay. RESULTS: Multivariate analysis adjusted for age demonstrated that in men, body-fat ratio was high, and HDL cholesterol level was low in A allele carriers of G-395A compared with GG. In women, glucose was high in A allele carriers of G-395A compared with GG, and also in T allele carriers of C1818T compared with CC. When divided into 2 groups according to age, in men <60 y, body mass index, body-fat ratio and waist circumference were high in A carriers of G-395A compared with GG. In women <60 y, bone mineral density was high in A allele carriers of G-395A compared with GG, and systolic blood pressure and glucose were high in T carriers of C1818T compared with CC. CONCLUSIONS: KLOTHO gene SNPs G-395A and C1818T are associated with lipid metabolism in men, and glucose metabolism, bone mineral density and systolic blood pressure in women.

Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population.

Gout based on hyperuricemia is a common disease with a genetic predisposition, which causes acute arthritis. The ABCG2/BCRP gene, located in a gout-susceptibility locus on chromosome 4q, has been identified by recent genome-wide association studies of serum uric acid concentrations and gout. Urate transport assays demonstrated that ABCG2 is a high-capacity urate secretion transporter. Sequencing of the ABCG2 gene in 90 hyperuricemia patients revealed several nonfunctional ABCG2 mutations, including Q126X. Quantitative trait locus analysis of 739 individuals showed that a common dysfunctional variant of ABCG2, Q141K, increases serum uric acid. Q126X is assigned to the different disease haplotype from Q141K and increases gout risk, conferring an odds ratio of 5.97. Furthermore, 10% of gout patients (16 out of 159 cases) had genotype combinations resulting in more than 75% reduction of ABCG2 function (odds ratio, 25.8). Our findings indicate that nonfunctional variants of ABCG2 essentially block gut and renal urate excretion and cause gout.

Controls for monitoring the deterioration of stored blood samples in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study).

Cohort studies commonly store blood samples to measure the associations of biomarkers with disease risks for a long time after the study subjects are enrolled. To obtain valid measurements of the stored samples, monitoring their degree of deterioration is essential. The first stage of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study launched in 2005 included a project to validate the quality of stored blood samples. This project will compare the measurements of representative molecules over different storage periods (1, 4, and 8 years after sampling, and when a nested case-control study is conducted), different storage temperatures (-80 and -150 degrees C), and different separation conditions (temperature and time) before storage. For these purposes, 28 ml of peripheral blood from 10 people was sampled four times annually, using two tubes for serum and two EDTA-Na tubes for plasma. These samples were treated using the process adopted for the J-MICC study protocol, and stored in tubes containing 300 microliters of serum or plasma labeled with two-dimensional bar codes. The sampling was started in 2006, and some of the specimens will be stored until the end of the J-MICC Study in 2035. The resulting findings will produce valuable information on the stability of the molecules, not only for the J-MICC Study, but also for other cohort studies.

Smoking and serum CA19-9 levels according to Lewis and secretor genotypes.

CA19-9, a marker for cancers of biliary tract, pancreas and colorectum, is not synthesized in those with no enzyme activity genotype (le/le) of Lewis (Le) gene. No enzyme activity genotype (se/se) of secretor (Se) gene is known to have an association with high serum CA19-9 levels. There are also variations in serum CA19-9 levels independent of the genotypes. This study aimed to examine the associations of serum CA19-9 levels with smoking, alcohol drinking and body mass index (BMI; kg/m(2)), after the adjustments of Le and Se genotypes. Subjects were 486 health check-up examinees (158 males and 328 females) aged from 39 to 90 years in Hokkaido, Japan. Genotyping was conducted for 3 polymorphisms; Le T59G (59T for Le allele and 59G for le allele), Se A385T (385A for Se allele and 385T for sej allele), and Se pseudogene (se5 allele). The genotypes of Le and Se were deterministic factors of serum CA19-9. Those with Le/Le & se/se had the highest mean, while CA19-9 was not detected or very low in those with le/le. Although no associations were observed with alcohol drinking and BMI, a significant association was observed with smoking. Among those with Le/Le, the geometric mean of CA19-9 was significantly lower for current smokers than for noncurrent smokers (p = 0.011 in 4-way ANOVA with age, sex and Se genotype). When hemoglobin A1c was further adjusted, the association became stronger (p = 0.0027). In addition to polymorphic variations, some components of cigarette smoke may influence the production or destruction of CA19-9.

Metabolic syndrome defined by new criteria in Japanese is associated with increased liver enzymes and C-reactive protein.

Metabolic syndrome (MetS) is characterized by the presence of atherogenic risk factors, and is associated with a marked increase in the risk of cardiovascular disease. Recently, the criteria of MetS were newly defined in Japan. We examined the relationship between MetS and the various metabolic parameters in Japanese subjects. This study included 458 Japanese subjects undergoing medical checkups at Nagoya University Hospital. New criteria developed by the joint committee of eight Japanese medical societies for the clinical recognition of MetS were adopted. We examined the association between MetS and various metabolic parameters, including liver enzymes (alanine aminotransferase, ALT; gamma glutamyltransferase, GGT) and highly sensitive C-reactive protein (hsCRP). The mean overall prevalence of MetS was 8.7% (male: 12.9%; female: 2.2%, p = 0.0001). MetS was significantly associated with elevated ALT (> 45 IU/L) (OR: 3.37, 95% CI: 1.19-9.52, p < 0.05) and GGT (> 64 IU/L in males, > 45 IU/L in females) (OR: 4.96, 95% CI: 2.31-10.66, p = 0.0001), respectively. MetS was also significantly associated with elevated hsCRP (> or = 0.1 ng/mL) (OR: 2.77, 95% CI: 1.20-6.41, p < 0.05). Thus, MetS was associated with elevated liver enzymes (especially, GGT), and inflammation (hsCRP).

Significant association between Helicobacter pylori infection and serum C-reactive protein.

BACKGROUND: Helicobacter pylori (H. pylori) infection in gastric mucosa may cause systemic inflammatory reaction. This study aimed to examine the association between the infection and serum high sensitivity C-reactive protein (hsCRP). METHODS: Subjects were comprised of three groups; 453 health checkup examinees from Yakumo town inhabitants in Hokkaido, Japan (YTI, 153 males and 300 females), 449 health checkup examinees (ENUH, 273 males and 176 females), and 255 female patients of an infertility clinic (PIC), Nagoya University Hospital. Twenty participants with hsCRP more than 1 mg/dl were excluded from the analysis. Those with hsCRP more than 0.1mg/dl were defined as high hsCRP individuals. H. pylori infection status was examined with a serum IgG antibody test. RESULTS: When the three groups were combined, the geometric mean of hsCRP concentration was significantly higher among the seropositives (0.047 mg/dl) than among the seronegatives (0.035 mg/dl); p<0.0001 by a t-test. The percentage of high hsCRP individuals was also higher in the seropositives than in the seronegatives among any group; 23.3% and 20.1% in YTI, 22.0% and 16.0% in ENUH, and 32.7% and 18.7% in PIC, respectively, although the difference was significant only in ENUH. The summary odds ratio of the high hsCRP for the seropositives relative to the seronegatives was 1.38 (95% confidence interval, 1.01-1.89), when age, sex, body mass index, smoking, and subject group were adjusted by a logistic model. CONCLUSIONS: In three groups, hsCRP was higher among the infected individuals. The summary odd ratio indicated that H. pylori infection could influence the serum hsCRP level.

Associations between a PTPN11 polymorphism and gastric atrophy--opposite in Uzbekistan to that in Japan.

Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) of gastric epithelial cells interacts with cagA from Helicobacter pylori (H. pylori). Our previous studies found the AA genotype of a G/A single nucleotide polymorphism at intron 3 (rs2301756) of PTPN11 gene, which encodes SHP-2, to be associated with a lower risk of gastric atrophy. The present study aimed to examine the association with gastric atrophy among the subjects of a case-control study of peptic ulcer disease (PUD) conducted in the Uzbek Republic. Cases were 95 patients (61 males and 34 females) with PUD aged 16 to 85 years. Controls were 102 hospital volunteers (42 males and 60 females) including 42 patients with miscellaneous diseases, aged 15 to 75 years. Gastric atrophy was evaluated with serum pepsinogens (PG1<70 ng/ml and PG1/PG2<3). Polymorphisms of PTPN11 at intron 3 (rs2301756) and intron10 (rs12229892) were genotyped with PCR with confronting two-pair primers (PCR-CTPP). Anti-cagA IgG antibody was detected in 93.7% of cases and 77.5% in controls. Gastric atrophy was observed in 24.2% of the PUD patients and 33.3% in the controls. The A allele at intron 3 was completely linked to the G allele at intron 10. The age, sex, and group (cases and controls) adjusted odds ratio of gastric atrophy was 0.18 (95% confidence interval, 0.04-0.86) for intron 3 GG genotype relative to AA genotype. Since the finding was opposite to that among Japanese, the H. pylori strains and/or lifestyle in Uzbekistan might modify the association.

Serum folate and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism adjusted for folate intake.

BACKGROUND: Serum folate concentration is lower in individuals with the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype than in those with the MTHFR 677CC or 677CT genotypes. Since studies considering folate intake are limited, we examined the association between folate intake and serum folate levels, according to the genotype. METHODS: The subjects comprised 170 Japanese persons (74 males and 96 females) aged 20-75 years who visited a clinic to test for Helicobacter pylori infection. Folate intake was estimated using a semiquantitative food frequency questionnaire, and serum folate was measured in the residual fasting blood samples of the subjects. MTHFR C677T was genotyped using polymerase chain reaction. RESULTS: The geometric means of serum folate level were 6.19, 6.20, and 5.17 ng/mL among the 60 participants with the 677CC genotype, 90 participants with the 677CT genotype, and 20 participants with the 677TT genotype, respectively. No difference was noted in the mean folate intake estimated using the food-frequency questionnaire. Regression analysis showed that log(e)(serum folate) adjusted for age, sex, and log(e)(folate intake) was significantly lower among those with the 677TT genotype than among those with the 677CT or 677CC genotypes (p = 0.01). The adjusted reduction in serum folate was 20.2% (95% confidence interval, 5.4-32.6%) in the case of the 677TT genotype relative to the levels in the case of the 677CC/677CT genotypes. When folate intake was adjusted for total energy intake, using the residual method, the slope of the regression line for 677TT was smaller than those of the regression lines for 677CC and 677CT. CONCLUSION: Individuals with the 677TT genotype may need to consume more folate to maintain serum folate levels similar to those found in individuals with the 677CC/677CT genotypes.

Active smoking, passive smoking, and breast cancer risk: findings from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk.

BACKGROUND: Evidence is lacking regarding the relationship between cigarette smoking and breast cancer in Japanese women. We examined the association between breast cancer incidence and active and passive smoking in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. METHODS: Our study comprised 34,401 women aged 40-79 years who had not been diagnosed previously with breast cancer and who provided information on smoking status at baseline (1988-1990). The subjects were followed from enrollment until December 31, 2001. Cox proportional-hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between breast cancer incidence and tobacco smoke. RESULTS: During 271,412 person-years of follow-up, we identified 208 incident cases of breast cancer. Active smoking did not increase the risk of breast cancer, with a HR for current smokers of 0.67 (95% CI: 0.32-1.38). Furthermore, an increased risk of breast cancer was not observed in current smokers who smoked a greater number of cigarettes each day. Overall, passive smoking at home or in public spaces was also not associated with an increased risk of breast cancer among nonsmokers. Women who reported passive smoking during childhood had a statistically insignificant increase in risk (HR: 1.24; 95% CI: 0.84-1.85), compared with those who had not been exposed during this time. CONCLUSION: Smoking may not be associated with an increased risk of breast cancer in this cohort of Japanese women.

Modification of the effect of smoking on cholesterol in Japanese carriers of a PTPN11 polymorphism.

A widely-expressed protein tyrosine phosphatase, SHP-2, regulates apoB secretion by insulin. We hypothesised that a variation in the SHP-2 gene, PTPN11, may interact with smoking to influence serum lipid concentrations. The study comprised 794 subjects (278 males and 516 females), aged 39-88 years, who attended a health examination in Hokkaido, Japan in 2003. Subjects were genotyped for a G/A PTPN11 polymorphism (rs2301756). The mean serum LDL cholesterol, HDL cholesterol and triglyceride levels, stratified by genotype, were compared between current and non- (never or ex-) smokers. Among the AA genotype carriers, LDL cholesterol levels were significantly decreased in current vs. non-smokers [mean ± SD, 101±34 mg/dl vs. 146±40 mg/dl; b (adjusted mean difference) = -56.0; 95% CI -102.8 to -9.3; p=0.019 after adjustment for age, sex and body mass index]. In contrast, HDL cholesterol levels were increased in current vs. non-smokers (66±5 mg/dl vs. 58±12 mg/dl; b=14.9; 95% CI 3.1 to 26.8; p=0.014 after adjustment). The interaction between a current smoking habit and the AA genotype had a significant effect on LDL and HDL cholesterol (LDL-C, p=0.039; HDL-C, p=0.020). These data suggest that cigarette smoking might alter the metabolism of cholesterol in Japanese PTPN11 AA genotype carriers.

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 m(2)) 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 m(2); 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.

Consumption of soy foods and the risk of breast cancer: findings from the Japan Collaborative Cohort (JACC) Study.

OBJECTIVE: The association between a lower incidence of breast cancer within the Asian population and the consumption of a diet high in soy has recently been the subject of much attention. To examine whether soy foods really have protective effects against breast cancer and how their influence on breast cancer is modified according to menopausal status, we conducted a population-based, prospective cohort study in Japan. METHODS: We analyzed the data from the Japan Collaborative Cohort (JACC) Study. From 1988 to 1990, 30,454 women aged 40-79 years, completed a questionnaire on diet and other lifestyle features. Hazard ratios (HRs) were computed to examine the association between soy intake and the risk of breast cancer. RESULTS: During the mean follow-up of 7.6 years, 145 cases of breast cancer were documented. We found no significant association between the risk of breast cancer and consumption of tofu, boiled beans, and miso soup; the multivariate HRs (95% CI) in the highest category of consumption were 1.14 (0.74-1.77), 0.77 (0.47-1.27) and 1.01 (0.65-1.56), respectively. Only among postmenopausal women, we found no significant associations between soy foods and the risk of breast cancer. CONCLUSIONS: This prospective study suggests that consumption of soy food has no protective effects against breast cancer. Further large-scale investigations eliciting genetic factors may clarify different roles of various soybean-ingredient foods on the risk of breast cancer.

Elevated C-reactive protein levels in patients with polypoidal choroidal vasculopathy and patients with neovascular age-related macular degeneration.

PURPOSE: To determine the relationship between systemic C-reactive protein (CRP) levels and polypoidal choroidal vasculopathy (PCV) and advanced neovascular age-related macular degeneration (AMD) in Japanese patients. DESIGN: Case-control study. PARTICIPANTS: Ninety-seven patients with PCV, 176 with advanced neovascular AMD, and 262 control subjects without any macular abnormality were studied. METHODS: Color fundus photographs of the macular area were taken from both eyes in all subjects. Indocyanine green angiography and fluorescein angiography were performed for diagnosis. The CRP level was measured by a high-sensitivity assay using a latex aggregation immunoassay, and the levels in patients with PCV and neovascular AMD were compared with that in the control group using the Kruskal-Wallis test. Associations between CRP and PCV or neovascular AMD were compared using logistic regression analysis by computing the odds ratios (ORs) and 95% confidence intervals (CIs) after the study populations were divided into quartiles. MAIN OUTCOME MEASURES: The CRP levels in patients with PCV, patients with neovascular AMD, and control subjects. Standard univariate and multivariate analyses between groups. RESULTS: Median CRP levels were significantly higher in cases with PCV (0.94 mg/l) or with advanced neovascular AMD (0.95 mg/l) than in control subjects (0.43 mg/l) (P<0.001 for Kruskal-Wallis test). After adjusting for baseline characteristics such as age, gender, smoking status, alcohol use, body mass index, history, and use of antiinflammatory drugs, the increase in risk was significant for the highest quartile of CRP for both PCV (OR, 3.53; 95% CI, 1.49-8.40) and neovascular AMD (OR, 4.08; 95% CI, 1.94-8.56), and for the third quartile of CRP for neovascular AMD (OR, 2.29; 95% CI, 1.07-4.91). The trends for an increase in risk of disease with increase in CRP were statistically significant for both PCV (P = 0.001) and neovascular AMD (P<0.001). CONCLUSIONS: The significant associations between elevated serum CRP levels and PCV or neovascular AMD in the Japanese strongly suggest that inflammatory processes are involved in the pathogenesis of PCV and neovascular AMD.

Psychological attitudes and risk of breast cancer in Japan: a prospective study.

OBJECTIVE: To examine the association between psychological factors and the risk of breast cancer prospectively in a non-Western population. METHODS: Data from the Japan Collaborative Cohort (JACC) study were analyzed. From 1988 to 1990, 34,497 women aged 40-79 years completed a questionnaire on medical, lifestyle and psychosocial factors. The rate ratios (RRs) of their responses were computed by fitting to proportional hazards models. RESULTS: During the mean follow-up period of 7.5 years, 149 breast cancer cases were documented. Those individuals who possessed "ikigai" (Japanese term meaning something that made one's life worth living) showed a significantly lower risk of breast cancer (multivariate-adjusted RR=0.66; 95% confidence interval [CI]=0.47-0.94). Those who perceived themselves as able to make decisions quickly also had a lower risk of breast cancer (multivariate-adjusted RR=0.56; 95% CI=0.36-0.87). The other factors investigated, including ease of anger arousal and self-perceived stress of daily life were not associated with breast cancer risk. CONCLUSIONS: Although further studies will be necessary to verify these findings, our results suggest that having "ikigai" and being decisive decrease an individual's subsequent risk of breast cancer.

No association between Helicobacter pylori seropositivity and ornithine decarboxylase (ODC) A317G polymorphism, and no modification by NAD(P)H:qinone oxidoreductase 1 (NQO1) C609T.

Our previous epidemiologic study reported that NAD(P)H:quinone oxidoreductase 1 (NQO1) 609C/C with full enzyme activity was a high risk genotype for Helicobacter pylori (H. pylori) seropositivity. Since NQO1 stabilizes ornithine decarboxylase (ODC), which attenuates the innate immune response through elevated polyamines, ODC functional polymorphisms may also influence H. pylori seropositivity. This study aimed to examine the association with ODC A317G polymorphism, as well as the modification by NQO1 C609T. The two polymorphisms were determined by polymerase chain reaction with confronting two-pair primers (PCR-CTPP) among 465 health checkup examinees in Nagoya. The ODC A317G genotype frequency was 35.9% for A/A, 49.3% for A/G, and 14.8% for G/G. The sex-age-adjusted odds ratio (OR) of the ODC gene for H. pylori seropositivity was not significant (OR = 1.09 for G/A and OR = 1.02 for G/G, relative to A/A). Among subjects with any NQO1 genotype, no association was observed between the ODC ploymorphism and H. pylori seropositivity. Results of the present study did not support the hypothesis that the different genetic traits in the ODC-polyamine pathway are associated with susceptibility to persistent H. pylori infection. The higher frequency of the ODC 317A allele in the Japanese population than that in the Caucasian population is firstly reported. The genetic traits through the ODC-polyamine pathway will be further investigated.

No associations of Helicobacter pylori infection and gastric atrophy with plasma total homocysteine in Japanese.

Recent studies have suggested that Helicobacter pylori (H. pylori) infection might be a risk factor for atherosclerosis. Since the bacterium has not been isolated from atherosclerotic lesions, a direct role in atherogenesis is not plausible. We examined associations of plasma total homocysteine (tHcy) and serum folate, independent risk factors for atherosclerosis, with H. pylori infection and subsequent gastric atrophy among 174 patients (78 males and 96 females) aged 20 to 73 years, who visited an H. pylori eradication clinic of Nagoya University from July 2004 to October 2005. Polymorphism genotyping was conducted for methylenetetrahydrofolate reductase (MTHFR) C677T and thymidylate synthase (TS) 28-bp tandem repeats by PCR with confronting two-pair primers and PCR, respectively. H. pylori infection and gastric atrophy were not significantly associated with hyperhomocysteinemia (tHcy > or = 12 nmol/ml), when adjusted by sex, age, smoking, alcohol, and genotypes of MTHFR and TS. The adjusted odds ratio of gastric atrophy for low folate level (< or = 4 mg/ml) was 0.21 (95% confidence interval = 0.05-0.78). The associations of tHcy with serum folate and MTHFR genotype were clearly observed in this dataset. The present study demonstrated that folate and MTHFR genotype were the deterministic factors of plasma tHcy, but not H. pylori infection and subsequent gastric atrophy, indicating that even if H. pylori infection influences the risk of atherosclerosis, the influence may not be through the elevation of homocysteine.

Alternative genotyping method of GSTT1 null/present polymorphism.

Glutathione S-transferase (GST) theta is an enzyme to detoxify xenobiotic compounds. The gene GSTT1 has a null/present polymorphism in one of the targets for cancer susceptibility research. The polymorphism is classified into two types: present type with at least one present allele (heterozygote and homozygote) and null type without a present allele. Although one report showed a method to distinguish the heterozygote from the present homozygote, its use has been limited possibly owing to the difficulty of successful genotyping of long DNA sequences (1460 base pairs). This article reports an alternative method utilizing typical PCR primers specific to the null allele (566 base pairs) and the present allele (458 base pairs). All samples of the GSTT1 null genotype processed by the present PCR method (n = 331), were correctly classified as the null genotype by a conventional method, and the samples of heterozygous (n = 364) or present homozygous (n = 108) genotype as the present genotype; this indicates that it is appropriate for future research to utilize three genotypes of the GSTT1 null/present polymorphism.