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Abstract Background Nitric oxide is a key molecule not only in the cardiovascular system, but also in the metabolic-endocrine system. The purpose of this study was to examine possible associations of the NOS3 T-786C polymorphism (rs2070744) with serum lipid levels on the basis of lifestyle factors for tailoring prevention of dyslipidemia. Methods For this cross-sectional study, a total of 2226 subjects aged 35 to 69 years (1084 men and 1142 women) were selected from Japanese participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. They were recruited in eight areas throughout Japan between February 2004 and November 2008. Results In a stratified analysis by leisure-time physical activity, the likelihood of hypertriglyceridemia (serum triglyceride levels ≥ 150 mg/dL) among subjects with the C allele was significantly lower than those without it in the active group (OR = 0.43, 95% CI = 0.22-0.84 in the fasting group), but not in the sedentary group. A gene-environment interaction between the T-786C polymorphism and leisure-time physical activity for hypertriglyceridemia was significant (P = 0.007 in the fasting group). Additionally, serum triglyceride levels (mean ± SD) across leisure-time physical activity classes decreased significantly only in the TC + CC genotype group (111 ± 60 mg/dL for sedentary, 95 ± 48 mg/dL for moderately active, 88 ± 44 mg/dL for very active, P for trend = 0.008 in the fasting group), but not in the TT genotype group. Total cholesterol, high-density lipoprotein (HDL) cholesterol, and non-HDL cholesterol levels had no significant association with the polymorphism. Conclusions This study suggests that the NOS3 T-786C polymorphism modifies the effect of leisure-time physical activity on serum triglyceride levels.

Abstract Background The aim of this study was to explore the associations between common potential functional promoter polymorphisms in pro-/anti-inflammatory cytokine genes and kidney function/chronic kidney disease (CKD) prevalence in a large Japanese population. Methods A total of 3,323 subjects aged 35-69 were genotyped for all 10 single nucleotide polymorphisms (SNPs) in the promoter regions of candidate genes with minor allele frequencies of > 0.100 in Japanese populations. The estimated glomerular filtration rate (eGFR) and CKD prevalence (eGFR < 60 ml/min/1.73 m2) of the subjects were compared among the genotypes. Results A higher eGFR and lower prevalence of CKD were observed for the homozygous variants of IL4 -33CC (high IL-4 [anti-inflammatory cytokine]-producing genotype) and IL6 -572GG (low IL-6 [pro-inflammatory cytokine]-producing genotype). Subjects with IL4 CC + IL6 GG showed the highest mean eGFR (79.1 ml/min/1.73 m2) and lowest CKD prevalence (0.0%), while subjects carrying IL4 TT + IL6 CC showed the lowest mean eGFR (73.4 ml/min/1.73 m2) and highest CKD prevalence (17.9%). Conclusions The functional promoter polymorphisms IL4 T-33C (rs2070874) and IL6 C-572G (rs1800796), which are the only SNPs that affect the IL-4 and IL-6 levels in Japanese subjects, were associated with kidney function and CKD prevalence in a large Japanese population.

Abstract Background Although SLC22A12 258X allele was found among those with hypouricemia, it was unknown that serum uric acid distribution among those with SLC22A12 258X allele. This study examined serum uric acid (SUA) distribution according to SLC22A12 W258X genotype in a general Japanese population. Methods Subjects were 5,023 health checkup examinees (3,413 males and 1,610 females) aged 35 to 69 years with creatinine < 2.0 mg/dL, who were participants of a cohort study belonging to the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). SLC22A12 W258X was genotyped with a polymerase chain reaction with confronting two-pair primers. Results The genotype frequency was 4,793 for WW, 225 for WX, and 5 for XX, which was in Hardy-Weinberg equilibrium (p = 0.164) with X allele 0.023 (95% confidence interval [0.021-0.027]). Mean (range) SUA was 6.2 (2.1-11.4) mg/dL for WW, 3.9 (0.8-7.8) mg/dL for WX, and 0.8 (0.7-0.9) mg/dL for XX among males, and 4.5 (1.9-8.9) mg/dL, 3.3 (2.0-6.5) mg/dL, and 0.60 (0.5-0.7) mg/dL among females, respectively. Six individuals with SUA less than 1.0 mg/dL included two males with XX genotype, one male with WX genotype, and three females with XX genotype. Subjects with WX genotype were 14 (77.8%) of 18 males with a SUA of 1.0-2.9 mg/dL, and 28 (34.6%) of 81 females with the same range of SUA. The corresponding values were 131 (25.1%) of 522 males and 37 (3.5%) of 1,073 females for SUA 3.0-4.9 mg/dL, and 8 (0.4%) of 2,069 males and 5 (1.1%) of 429 females for SUA 5.0-6.9 mg/dL. The X allele effect for SUA less than 3 mg/dL was significantly (p < 0.001) higher in males (OR = 102.5, [33.9-309.8]) than in females (OR = 25.6 [14.4-45.3]). Conclusions Although SLC22A12 W258X was a determining genetic factor on SUA, SUA of those with WX genotype distributed widely from 0.8 mg/dL to 7.8 mg/dL. It indicated that other genetic traits and/or lifestyle affected SUA of those with WX genotype, as well as those with WW genotype.

Abstract Background Metabolic syndrome (MetS) is potentially effective measures to identify individuals at risk of coronary heart disease (CHD) and type 2 diabetes. To verify the hypothesis that smoking cessation may increase the risk of MetS, a follow-up study taking drinking habit into account was conducted for the examinees at one health checkup institution. Methods Subjects were the examinees who visited the Institution for Disease Prevention and Health Checkup, Seirei Mikatabara Hospital for annual health checkup from January 2003 to December 2006. Among them, 5,872 smokers (5,479 men, 93.3%) free from MetS at the first year in two consecutive years were selected. For the long term follow-up, the risk of MetS among those who maintained their nonsmoking status for 1 or 2 additional years was evaluated. Results Relative to non-quitters, quitters showed a significantly elevated adjusted hazard ratio (aHR) of MetS in two consecutive years (aHR = 2.09, 95% confidence interval: 1.43–3.04, P < 0.001). The aHR was higher among the quitters who had a drinking habit at the first year (aHR = 2.42, 95% CI: 1.48–3.94, P < 0.001). Analyses for 1 or 2 additional years of follow-up revealed that this significant increase in risk of MetS was transient. Conclusion The present study revealed that smoking cessation elevated the risk of MetS significantly, especially among drinkers. Although this detrimental effect of smoking cessation was found to be during only a short term, our results suggested that we should take measures, presumably including interventions for alcohol cessation, not to expose smoking quitters to this adverse effect. Further investigations are required to confirm our findings.

Abstract Background Previous studies have revealed the significance of Helicobacter pylori (H. pylori) infection as a risk factor of gastric cancer. Cytotoxin-associated gene A (cagA) positivity has been demonstrated to determine the clinical outcome of H. pylori infection in the presence of SHP-2 (src homology 2 domain-containing protein tyrosine phosphatase-2). This study aimed to examine the formerly reported association of G/A PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) polymorphism (rs2301756) with gastric atrophy, as well as the association with gastric cancer in a Japanese population using a large sample size. Methods Study subjects were 583 histologically diagnosed patients with gastric cancer (429 males and 154 females) and age- and sex-frequency-matched 1,636 non-cancer outpatients (1,203 males and 433 females), who visited Aichi Cancer Center Hospital between 2001–2005. Serum anti-H. pylori IgG antibody and pepsinogens were measured to evaluate H. pylori infection and gastric atrophy, respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a logistic model. Results Among H. pylori seropositive non-cancer outpatients, the age- and sex-adjusted OR of gastric atrophy was 0.82 (95% CI 0.62–1.10, P = 0.194) for G/A, 0.84 (95% CI 0.39–1.81, P = 0.650) for A/A, and 0.83 (95% CI 0.62–1.09, P = 0.182) for G/A+A/A, relative to G/G genotype, and that of severe gastric atrophy was 0.70 (95% CI 0.47–1.04, P = 0.079), 0.56 (95% CI 0.17–1.91, P = 0.356), and 0.68 (95% CI 0.46–1.01, P = 0.057), respectively. Among H. pylori infected subjects (H. pylori seropositive subjects and seronegative subjects with gastric atrophy), the adjusted OR of severe gastric atrophy was further reduced; 0.62 (95% CI 0.42–0.90, P = 0.012) for G/A+A/A. The distribution of the genotype in patients with gastric cancer was not significantly different from that for H. pylori infected subjects without gastric atrophy. Conclusion Our study results revealed that those with the A/A genotype of PTPN11 rs2301756 polymorphism are at lower risk of severe gastric atrophy, but are not associated with a decreased risk of gastric cancer, which partially supported our previous finding that the polymorphism in the PTPN11 gene encoding SHP-2 was associated with the gastric atrophy risk in H. pylori infected Japanese. The biological roles of this PTPN11 polymorphism require further investigation.

Abstract Background Sufficient targeted HIV prevention activities aiming at reducing HIV transmission within and from an extremely marginalized population of injection drug users (IDUs) must urgently and efficiently be implemented in Vietnam. This study was conducted to facilitate the development of such activities by describing transmission risks of young IDUs and evaluating factors in association with HIV infection. Methods Thirty clusters were selected from 29 hotspot communes in Long An province by probability proportional to size (PPS) sampling method. The snowball technique was used for enrolling participants in each cluster. The cross-sectional association of factors obtained during direct structured interviews to 248 male IDUs aged 14 to 29 years old and with their HIV test results were examined. Results The HIV prevalence among the studied IDUs was 32%. Age range of 18–20 years old, low educational level, sharing injection equipment or injection drug use in the other cities were independently associated with HIV serostatus in the multivariate analysis. Sexual behaviors did not differ between HIV-positive and -negative IDUs. Among HIV seropositive IDUs who had sexual contact with primary (n = 37), casual (n = 6), and commercial (n = 15) partners, only 5.4% (n = 2), 33.3% (n = 2), and 46.7% (n = 7), respectively, responded that they had used condoms every time. Conclusion About one-third of young IDUs aged less than 30 identified in the hotspot communes in Long An, Vietnam was found to be infected with HIV, and socio-demographic and injection-related factors might account for the infection risk. Prevailing risky sexual behavior of this extremely marginalized population highlights the need to reduce their high transmission risks as a public health priority.