Matrix metalloproteinase 9 gene polymorphisms are associated with a multiple family history of gastric cancer.

BACKGROUND: A family history of gastric cancer (GC) is a well-known risk factor of GC. Genetic variations in genes of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been related to the risk of GC, but their association with familial background is not clear. We investigated whether individuals with a multiple family history of GC have more risk genotypes of MMP/TIMP genes. METHODS: We genotyped ten common functional polymorphisms of MMP/TIMP genes in 4427 individuals aged 35-69 years without a history of GC who were enrolled in the Japan Multi-institutional Collaborative Cohort Study. Individuals who have two or more first-degree relatives (parents and siblings) with GC were categorized as having a multiple family history. Odds ratios (ORs) for multiple family history compared with no family history were calculated. RESULTS: MMP9 279QQ (rs17576) was more frequently observed in individuals whose both parents had a history of GC (n = 23) and in individuals for whom one parent and their sibling(s) had a history of GC (n = 36) compared with those with no family history (n = 3816) [30.4 % vs 11.6 %, OR 4.34, 95 % confidence interval (CI) 1.45-13.03 and 16.7 % vs 11.6 %, OR 2.26, 95 % CI 0.81-6.27 after adjustment for age, sex, and current smoking]. The population attributable fraction was 38.1 %. The haplotype MMP9-1562C/279Q/668Q was more frequently observed in individuals whose both parents had a history of GC and in individuals for whom one parent and their sibling(s) had a history of GC compared with those with no family history (OR 3.35, 95 % CI 0.75-14.96 and OR 3.51, 95 % CI 1.35-9.15 respectively). CONCLUSIONS: MMP9 polymorphisms were associated with a multiple family history of GC. Screening for these genotypes together with familial background may help us to identify individuals at an increased risk of GC.

Interactions between inflammatory gene polymorphisms and HTLV-I infection for total death, incidence of cancer, and atherosclerosis-related diseases among the Japanese population.

BACKGROUND: 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. METHOD: 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. RESULTS: 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). CONCLUSION: 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.

Polymorphisms of genes involved in lipid metabolism and risk of chronic kidney disease in Japanese - cross-sectional data from the J-MICC study.

BACKGROUND: Chronic kidney disease (CKD) is known to be one of the causes of cardiovascular disease and end-stage renal disease. Among the several treatable risk factors of CKD, that of dyslipidemia is relatively controversial. To clarify the association of polymorphisms in genes involved in lipid metabolism with the risk of CKD in the Japanese population, we used cross-sectional data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. METHODS: A total of 3,268 men and women, aged 35-69 years, were selected from J-MICC Study participants for inclusion in this study. Twenty-eight candidate single nucleotide polymorphisms (SNPs) were selected in 17 genes associated with the risk of lipid metabolism disorders, and genotyping of the subjects was conducted using the multiplex PCR-based invader assay. The prevalence of CKD was determined for stages 3-5 (defined as estimated glomerular filtration rate <60 ml/min/1.73 m2). RESULTS: Logistic regression analysis revealed that SNPs APOA5 T - 1131C (rs662799), APOA5 T1259C (rs2266788), TOMM40 A/G (rs157580), and CETP TaqIB (rs708272) were significantly associated with CKD risk in those individuals genotyped, with age- and sex-adjusted odds ratios (ORs) per minor allele (and 95% confidence intervals (CIs)) of OR 1.22 (95% CI: 1.06-1.39), 1.19 (1.03-1.37), 1.27 (1.12-1.45), and 0.81 (0.71-0.92), respectively. Analysis of the gene-environment interaction revealed that body mass index (BMI) was a significant effect modifier for APOA5 T - 1131C (rs662799) and a marginally significant effect modifier for APOA5 T/C (rs2266788), with the interaction between BMI ≥30 and individuals with at least one minor allele of each genotype of OR 10.43 (95% CI: 1.29-84.19) and 3.36 (0.87-13.01), respectively. CONCLUSIONS: Four polymorphisms in APOA5, TOMM40, and CETP were shown to be significantly associated with CKD risk, and a significant interaction between the two APOA5 SNPs and BMI on CKD risk was also demonstrated. This suggests the future possibility of personalized risk estimation for this life-limiting disease.

Rhynchophorus ferrugineus larvae: A novel source for combating broad-spectrum bacterial and fungal infections.

Antimicrobial resistance is a growing concern due to the growth of antibiotic-resistant microorganisms, which makes it difficult to treat infection. Due to its broad-spectrum antimicrobial properties against a diverse array of bacteria, both Gram-positive and Gram-negative bacteria, and fungi, Rhynchophorus ferrugineus larval antimicrobial peptides (AMPs) have demonstrated potential as antimicrobial agents for the treatment of microbial infections and prevention of antibiotic resistance. This study emphasizes the unexplored mechanisms of action of R. ferrugineus larvae against microorganisms. Among the most widely discussed mechanisms is the effect of AMPs in larvae in response to a threat or infection. Modulation of immune-related genes in the intestine and phagocytic capacity of its hemocytes may also affect the antimicrobial activity of R. ferrugineus larvae, with an increase in phenoloxidase activity possibly correlated with microbial clearance and survival rates of larvae. The safety and toxicity of R. ferrugineus larvae extracts, as well as their long-term efficacy, are also addressed in this paper. The implications of future research are explored in this paper, and it is certain that R. ferrugineus larvae have the potential to be developed as a broad-spectrum antimicrobial agent with proper investigation.

Positive Association of Plasma Homocysteine Levels with Cardio-Ankle Vascular Index in a Prospective Study of Japanese Men from the General Population.

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.

A polymorphism near MC4R gene (rs17782313) is associated with serum triglyceride levels in the general Japanese population: the J-MICC Study.

Previously reported associations of a common polymorphism near melanocortin-4 receptor (MC4R) gene (rs17782313) with BMI/obesity were inconsistent, especially in East Asia, and the associations of the polymorphism with serum lipid levels have not been fully elucidated. This study evaluated the association between rs17782313 and obesity-related traits and serum lipid levels in the general Japanese population. A total of 2,035 subjects (aged 35-69 years, 1,024 males and 1,011 females) enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We examined the associations between near MC4R polymorphism (rs17782313) and obesity-related traits [height, weight, body mass index (BMI), weight change from 20 years old], serum lipid levels (triglycerides, total and HDL-cholesterol), and intake of nutrients (total energy and macronutrients). Polymorphism of rs17782313 (minor C allele) was positively associated with serum triglyceride levels (P for trend = 0.020) adjusted for age and sex. Analysis using a general linear model revealed that the number of minor C alleles was positively associated with serum triglyceride levels after adjustment for age, sex, and potential confounders (P for trend = 0.004). Statistical significance did not change after further adjustment for total energy intake and BMI. There was no significant association between rs17782313 and obesity-related traits including BMI. Interactions between rs17782313 and sex, BMI, or total energy intake for triglyceride levels were not significant. To our knowledge, this study demonstrated for the first time that rs17782313 was associated with serum triglyceride levels in Asian population. Further studies are needed to confirm this result.