Polymorphisms of the formylpeptide receptor gene (FPR1) and susceptibility to stomach cancer in 1531 consecutive autopsy cases.

Formylpeptide receptor (FPR1) is involved in inflammation, which is important in the pathogenesis of diverse conditions, including common diseases and cancers. To date, little is known about the relationships between FPR1 and such diseases, aside from the fact that FPR1 is related to periodontitis, which is implicated in systemic diseases such as stomach cancer. We hypothesized that FPR1 polymorphisms related to periodontal disease may confer susceptibility to stomach cancer. Two single nucleotide polymorphisms (SNPs) in the second extracellular region and C-terminus of the formylpeptide receptor gene were analyzed in 1531 consecutive autopsy cases in the Japanese elderly. The tri-allelic SNP of rs1042229 was detected by modified melting temperature analysis. Homozygous K alleles of rs1042229 were associated with stomach cancer (Odds ratio [OR]=1.62, confidence interval [CI]=1.05-2.48, p=0.028). In the analysis of the recessive model of the K allele, FPR1 was associated with a high risk of stomach cancer (OR=1.73, CI=1.15-2.55, p=0.0075). The risk allele for stomach cancer pointed in the same direction as periodontitis. This is the first study to evaluate polymorphisms of the FPR1 gene in stomach cancer to find a positive association between these polymorphisms and stomach cancer. Further studies on the relationship between stomach cancer and the FPR1 gene are warranted.

Association of a cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) polymorphism with elevated hemoglobin A1(c) levels and the prevalence of metabolic syndrome in Japanese men: interaction with dietary energy intake.

Genome-wide association studies have identified the cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) gene as a novel risk factor for type 2 diabetes mellitus. Application of this genetic marker for prevention of type 2 diabetes and metabolic syndrome (MetS) in healthy populations has not yet been evaluated. The authors examined the effects of a CDKAL1 polymorphism (rs9465871) on metabolic phenotype and of gene-lifestyle (CDKAL1-energy intake) interaction on MetS in a cohort of apparently healthy Japanese men examined in 2003. The CC genotype of the CDKAL1 variant was associated with elevated glycosylated hemoglobin A1(c) (HbA1c) levels. The prevalence of MetS was 25.6% for CC and 16.3% for TT + CT (odds ratio = 2.18, 95% confidence interval: 1.06, 4.48; P = 0.035). When dietary energy intake was accounted for, the variant's effect on HbA1c was observed in the highest energy-intake group (mean: CC, 5.6% (standard deviation, 1.7); TT + CT, 5.0% (standard deviation, 0.5); P = 0.025). In addition, the positive association between HbA1c and energy intake was stronger in subjects with the CC genotype than in subjects with TT + CT. These results suggest that the interaction between the CDKAL1 polymorphism and dietary energy intake influences the dysglycemic phenotype leading to MetS, possibly through impaired insulin secretion. The CDKAL1 polymorphism may be a marker for MetS in the Japanese population.

Medical students' reflection on the family planning services at primary health clinics in Malaysia.

CONTEXT: Family planning is crucial for everyone within the reproductive age to promote the health and welfare of every member of the family. For the medical students, it is essential to have core knowledge, understanding of family planning concept, and competency in communication skills with the patients. The final-year medical students are posted in Maternal and Child Health Clinics for 3 weeks to gain the knowledge and practical experiences on the primary healthcare in the community. AIMS: The aim of this study was to explore the experiences of final-year medical students on family planning services offered at community clinics in Malaysia. SETTINGS AND DESIGN: This was qualitative study. SUBJECTS AND METHODS: This qualitative study used the data of the students' reflection written in the case reports on family planning. Coding, identification of subthemes, and themes were done by two researchers independently using RQDA software. STATISTICAL ANALYSIS USED: Thematic analysis. RESULTS: Final-year medical students who had exposure to the clinical services at primary care clinic, regarding Malay word (Klinik Kesihatan) gained the learning opportunities during family planning session such as learning by observation, clerking, and counseling the patients, understanding the barriers to utilizing services and learning for their self-improvement. These learning opportunities lead to developing the positive attitudes on their learning experiences and the positive attitudes toward the concept and services of family planning. CONCLUSIONS: To have the better understanding of family planning services and provide the better care to the community in the future, the clinical exposure at the primary care clinics should be promoted for medical students in Malaysia.

Knowledge and attitude of mandatory infectious disease notification among final year medical students.

BACKGROUND: Disease surveillance is one of the major components to combat against infectious diseases. As health-care professionals are indispensable to mandatory notifiable disease surveillance, their knowledge and attitudes toward infectious disease notification played an important role for timely and effective reporting to the surveillance system. Therefore, we aimed to determine the knowledge of mandatory notifiable infectious diseases in Malaysia and attitude towards infectious disease reporting among final year medical students. METHODS: A cross-sectional study was conducted from May to June 2017 in the private medical college in Malaysia. MATERIALS AND METHODS: We purposively selected the final year (semester 10) medical students and a total of 124 students participated in this study. We collected data using a self-administered, structured questionnaire. Data were analyzed using descriptive statistics, independent t-test, and one-way analysis of variance. RESULTS: Among the final year medical students, 47.5% had moderate knowledge but 4.2% had good knowledge of mandatory infectious disease notification. Only 3.2% of the students correctly answered all the notifiable diseases listed in the questionnaire. Most of the students had positive attitude toward communicable diseases reporting, rewards, and penalty for notification. There was no significant relationship between sociodemographic characteristics and knowledge and attitude of infectious disease notification. CONCLUSIONS: The majority of the final year medical students had moderate level of knowledge and positive attitude of infectious disease notification; however, there were some deficiencies. Better instruction and training on infectious disease notification procedures of Malaysia should be provided to the final year medical students which could not only reduce underreporting but also improve timely and effective reporting in future.

Knowledge, attitudes, and barriers toward research: The perspectives of undergraduate medical and dental students.

CONTEXT: Scientific research not only promotes health and combats diseases of an individual, but also it can strengthen the effectiveness of health systems. Hence, understanding of scientific methods becomes a crucial component in the medical profession. AIMS: This study was conducted to assess the knowledge, attitudes, and barriers toward research among undergraduate medical and dental students. SETTINGS AND DESIGN: This cross-sectional study was conducted among 295 undergraduate Bachelor of Medicine and Bachelor of Surgery (MBBS) and Bachelor of Dental Surgery (BDS) students from a private medical college in Malaysia. MATERIALS AND METHODS: We purposively selected 360 students attending the 3rd, 4th, and 5th year in MBBS course and BDS course in September 2015. A total of 295 students who were willing to provide written informed consent were included in this study. We collected data using a validated, self-administered, structured questionnaire which included 20 questions about knowledge toward scientific research, 21 attitude items in regard to scientific research, a list of 10 barriers toward conducting medical research, and 5 questions of confidence to conduct the medical research. STATISTICAL ANALYSIS USED: Data were analyzed using descriptive statistics, independent t-test, ANOVA, and multiple linear regression. RESULTS: Among the students, 56.9% had moderate knowledge while the majority (83.3%) had moderate attitude toward scientific research. The majorly cited barriers were the lack of time (79.9%), lack of knowledge and skills (72.1%), lack of funding (72.0%) and facilities (63.6%), and lack of rewards (55.8%). There was a significant association between age, academic year, and knowledge of research as the older age group, and 4th- and 5th-year students had higher knowledge score. The students of higher attitude score had better-perceived barriers score toward research with regression coefficient 0.095 (95% confidence interval 0.032-0.159). CONCLUSIONS: Even though the students had the positive attitudes toward scientific research, a supportive and positive environment is needed to improve skills and knowledge of research and to overcome the barriers toward the conduct of scientific research.

Epidemiological aspects of obesity and NASH/NAFLD in Japan.

Although the characteristics of non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD) have become well recognized, mainly in the clinical and pathological fields, epidemiological findings, including magnitude of the disease in a population (prevalence, outcomes, and mortality) and risk factors (relative risk and population attributable risk) are scarce in the Asia-Oceania region. Obesity is known to be one of the most important risk factors for NASH/NAFLD, and observed increases in NASH/NAFLD in selected areas or settings may be linked to the increase in overweight and obesity in Japanese adults in the last few decades. Obesity could be a major key to explaining NASH/NAFLD, because of the complex causal web that includes obesity, insulin resistance, dyslipidemia, high blood pressure, etc. In this paper epidemiological data on overweight and obesity were summarized as underlying factors for NAFLD with special reference to yearly trends and regional differences in the prevalence of obesity and overweight in Japanese adults using large-scale representative samples from the National Nutrition Surveys. Unfortunately, as very few published reports on population-based epidemiological data for NAFLD are currently available, we referred to selected data obtained from field settings to estimate the prevalence of NAFLD in the general population and its risk factors or associated factors. It is important to understand NASH/NAFLD as a common "burden of disease" in the populations if effective strategies to control these disorders are to be devised as part of public health initiatives.

Association between a polymorphism of aminolevulinate dehydrogenase (ALAD) gene and blood lead levels in Japanese subjects.

This cross-sectional study investigated the relationship between the aminolevulinate dehydrogenase (ALAD) genotype and blood lead levels among 101 Japanese workers. Blood lead concentration measurement, biomarkers, and genotyping were performed. The minor allele frequency (MAF) for ALAD (ALAD2) was 0.08. Although the blood lead level in the subjects with heterozygous GC genotype was significantly higher than those with homozygous GG genotype, there were no significant differences for hemoglobin, hematocrit, serum and urinary ALA levels among genotypes. ALAD2 genotype was significantly associated with the blood lead concentration, even in the environmental lead exposed subjects. Further confirmation with a large sample size is needed.

A functional SNP in ITIH3 is associated with susceptibility to myocardial infarction.

Myocardial infarction (MI) results from complex interactions of multiple genetic and environmental factors. To disclose genetic backgrounds of MI, we performed a large-scale, case-control association study using 52,608 gene-based single-nucleotide polymorphism (SNP) markers, and identified a candidate SNP located on chromosome 3p21.2-p21.1. Subsequent linkage-disequilibrium mapping indicated very significant association between MI and a SNP in exon 2 of the inter-alpha (globulin) inhibitor 3 gene (ITIH3; chi(2) = 24.88, P = 6.1 x 10(-7), 3,353 affected individuals versus 3,807 controls). In vitro functional analyses showed that this SNP enhanced the transcriptional level of the ITIH3 gene. Furthermore, we found expression of the ITIH3 protein in the vascular smooth muscle cells and macrophages in the human atherosclerotic lesions, suggesting ITIH3 SNP to be a novel genetic risk factor of MI.

Polymorphism of methylenetetrahydrofolate reductase gene (C677T MTHFR) is not a confounding factor of the relationship between serum uric acid level and the prevalence of hypertension in Japanese men.

BACKGROUND: The association between serum uric acid (UA) and the prevalence of hypertension, and the relationship between methylenetetrahydrofolate reductase (MTHFR) polymorphism and hypertension remains unclear. The aim of the present study was to investigate whether the C677T MTHFR mutation genotype (VV) is independently associated with the prevalence of hypertension or blood pressure (BP), and examined any interaction of MTHFR and UA with BP. METHODS AND RESULTS: Participants were randomly selected from all residents (aged 40-69 years) in a rural county of Japan, and the data for the men (n=335) were analyzed. ;Hypertension' was defined as systolic BP >or=140 and/or diastolic BP >or=90 mmHg and/or being administered antihypertensive medication. Serum UA level was independently associated with the prevalence of hypertension (odds ratio (95% confidence interval) =2.7 (1.2-5.9), p=0.047) for the highest tertile of serum UA (>or=398.5 micromol/L (6.7 mg/dl)) vs that of the lowest tertile (<321.2 micromol/L (5.4 mg/dl)), but the MTHFR mutation was not independently associated with prevalence of hypertension or BP. No interaction of the MTHFR mutation and serum UA with BP was found. CONCLUSIONS: The mutation of C677T MTHFR was not independently associated with the prevalence of hypertension or BP levels although serum UA was. Furthermore, the relationship between serum UA and BP was not modulated by the MTHFR mutation in Japanese men.

The 2.3 genotype of ESRRA23 of the ERR alpha gene is associated with a higher BMI than the 2.2 genotype.

ERR alpha (NR3B1) is an orphan nuclear receptor believed to be involved in energy metabolism and obesity. A 23-base pair sequence in the 5'-flanking region of the ERR alpha gene, referred to as ESRRA23, is polymorphic in human chromosomes. Here, we investigated the influence of the ESRRA23 polymorphism on obesity in 703 Japanese individuals by analyzing indices of obesity and related lifestyle factors. The frequency of genotypes was similar to that reported in whites. The 2.3-genotype was associated with a significantly higher BMI than was the 2.2-genotype. An increased number of ESRRA23 repeats may be a genetic factor in human obesity.

The relationships between plasma total homocysteine and selected atherosclerotic risk factors according to the C677T methylenetetrahydrofolate reductase gene in Japanese.

BACKGROUND: Variation of plasma total homocysteine (tHcy) levels among individuals is modified by 5,10-methylenetetrahydrofolate reductase (MTHFR) genotypes and selected atherosclerotic risk factors. DESIGN: Cross-sectional study. METHODS: Healthy Japanese men (n=213) and women (n=242) aged 40-69 years were examined. RESULTS: Serum uric acid, hemoglobin, hematocrit, serum creatinine, and men were independently significantly associated with plasma tHcy. The relationship between serum uric acid and plasma tHcy was the strongest in those with the mutant homozygote (VV), but the overall statistical test of interaction was not significant. CONCLUSIONS: Serum uric acid, hematocrit, hemoglobin, creatinine, and men were determinants of plasma tHcy levels. Further investigations are needed.

Epidemiological evidence that acetaldehyde plays a significant role in the development of decreased serum folate concentration and elevated mean corpuscular volume in alcohol drinkers.

BACKGROUND: Elevated mean corpuscular volume (MCV) is a traditional biological marker for alcohol abuse and alcoholism, but the underlying mechanism is unclear. Three recent epidemiologic studies consistently showed that MCV was elevated by alcohol drinking more markedly among individuals with genetically inactive aldehyde dehydrogenase-2 (ALDH2) (encoded by ALDH2*2 mutant allele) than those with active ALDH2 (encoded by ALDH2*1/2*1 genotype), suggesting that the elevated MCV was etiologically linked to acetaldehyde exposure. The purpose of the present study was to clarify further this relationship by examining the status of folate and vitamin B12. METHODS: The study participants were 159 men who were aged 40 to 69 years and randomly selected from a Japanese rural population. The genetic polymorphism of ALDH2 was determined by PCR-restriction fragment length polymorphism method; data on alcohol drinking and other lifestyles were collected using a structured questionnaire; serum concentrations of folate and vitamin B12 were measured using the protein competitive reaction method, and blood cell counts were measured by routine methods. A multiple linear regression model was used to analyze the data. RESULTS: : The relationship between alcohol drinking and serum folate concentration was significantly different between ALDH2 genotypes, indicating that the reduction of serum folate by alcohol drinking was more marked in men with ALDH2*1/2*2 than those with ALDH2*1/2*1. The relationship between alcohol drinking and elevated MCV was significantly stronger in men with ALDH2*1/2*2 than those with ALDH2*1/2*1 even after adjustment for serum folate and vitamin B12 concentrations. CONCLUSIONS: These findings indicate that acetaldehyde plays a significant role in the development of decreased serum folate concentration and elevated MCV by alcohol drinking.

Are the associations between life-style related factors and plasma total homocysteine concentration different according to polymorphism of 5,10-methylenetetrahydrofolate reductase gene (C677T MTHFR)? A cross-sectional study in a Japanese rural population.

Mild hyperhomocysteinemia is one of the known strong risk factors for atherosclerotic diseases, and therefore it is important to clarify factors that could determine plasma total homocysteine (tHcy) level. A cross-sectional study with a random sample of 455 Japanese rural residents aged 40-69 years was conducted in 2000 to investigate the associations of plasma tHcy concentration with 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and selected life-style related factors. The frequency of the mutant allele, Valine (V) allele, was 0.40 and the prevalence of VV genotype was 14.3%. Plasma tHcy concentration in VV was significantly higher than those in two other genotypes. There were significant inverse associations of plasma tHcy with serum folate and serum vitamin B12 (P<0.001 for trend, respectively); both being stronger in VV than in other genotypes. The number of cigarettes smoked per day was positively associated with plasma tHcy concentration. A multivariate regression analysis revealed that serum folate, serum vitamin B12, and MTHFR genotype were independently associated with plasma tHcy. The inter-individual variance of plasma tHcy was more explained by serum folate and vitamin B12 than by MTHFR genotype. Higher intakes of folate, vitamin B12, and non-smoking may be important to prevent mild hyperhomocysteinemia and the eventual atherosclerotic diseases in this Japanese rural population.