Possible association between oral health status and appetite loss in community-dwelling older adults.

This study aimed to evaluate the association between the oral health status and appetite in community-dwelling older adults. We enrolled 100 people aged ≥65 years who had participated in long-term care prevention projects between December 2018 and January 2019. Appetite was assessed using the Council on Nutrition Appetite Questionnaire score. The oral health status was assessed based on the number of teeth, occlusal condition, swallowing function, tongue coating, and the Oral Health Assessment Tool. A multiple linear regression analysis was performed with appetite as the dependent variable and each variable related to oral health status as an independent variable. The analysis was adjusted for sex, age, activities of daily living, cognitive function, smoking habit, and alcohol consumption. Dental pain was associated with poor appetite in community-dwelling older adults. No other oral health status parameter was associated with appetite. Thus, controlling dental pain is critical to prevent appetite loss while considering other factors.

Yogurt product intake and reduction of tooth loss risk in a Japanese community.

AIM: To evaluate the longitudinal association between yogurt product intake and oral health in a population-based study. MATERIALS AND METHODS: This study included 1967 Japanese residents aged 40-79 years who underwent dental examinations in 2012. Among them, 1469 participants were followed up in 2017 for the incidence of tooth loss, which was defined as two or more teeth lost over 5 years. The intake of yogurt products, defined as yogurt and lactic acid beverages, was estimated using a semi-quantitative food frequency questionnaire. The composition of the salivary microbiota was evaluated. RESULTS: The Poisson regression model showed that a higher intake of yogurt products was negatively associated with the incidence of tooth loss (p for trend = .020), adjusted for potential confounding factors. Mediation analysis confirmed that periodontal condition partly mediated the effect of yogurt product intake on tooth loss, while dental caries experience did not. Additionally, we confirmed the association of a high intake of yogurt products with a low percentage of the salivary microbiota pattern, which was associated with poor oral health. CONCLUSION: These findings suggest that the intake of yogurt products is associated with a lower risk of tooth loss resulting from periodontal disease, probably via modulation of the oral microbiome composition.

Baseline periodontal status and modifiable risk factors are associated with tooth loss over a 10-year period: Estimates of population attributable risk in a Japanese community.

BACKGROUND: This study aimed to examine whether modifiable risk factors can predict tooth loss over 10 years and estimate population attributable risk (PAR) for a combination of modifiable factors. METHODS: This longitudinal study included 1466 participants who underwent dental examinations in 2007 and 2017 and were aged 40 to 79 years at baseline. Periodontal conditions were assessed using the 2018 periodontal classification. Incident tooth loss was defined as ≥4 teeth lost over a 10-year period. We calculated the partial PAR (pPAR%) for tooth loss to estimate the combined effect of modifiable risk factors. RESULTS: Incidence of tooth loss was 17.5%. Directed acyclic graphs were used to identify risk factors for tooth loss. A logistic regression model showed that baseline periodontitis, dental caries experience, no regular dental visit, periodontal treatment, smoking, and obesity were associated with tooth loss after adjusting for covariates; pPAR% was 55.5% (95% confidence interval: 31.1% to 73.0%) in periodontitis Stage III to IV and 87.6% (50.4% to 97.4%) in the combination of all factors, respectively. The sex-stratified analysis showed that smoking and no regular dental visit in men and obesity in women were identified as potential risk factors for tooth loss. CONCLUSIONS: Modifiable factors accounted for most cases of incident tooth loss. Risk factors for tooth loss might differ by sex, suggesting that the appropriate approach for preventing tooth loss base on sex.

Number of teeth, denture wearing and cognitive function in relation to nutritional status in residents of nursing homes.

BACKGROUND: Although statistical associations between tooth loss and cognitive decline have been reported, there are few previous studies on denture wearing. Additionally, it remains unclear whether nutritional status mediates this association. OBJECTIVE: Our purpose was to test for the hypothesis that the association between the number of teeth and denture wearing with cognitive function is mediated by nutritional status in residents of nursing homes. MATERIALS AND METHODS: We enrolled 162 participants who required long-term care (mean age: 87.7 ± 7.5 years, 26 men and 136 women) and were admitted to eight nursing homes in Fukuoka city, from September 2013 to March 2014. A trained dentist conducted dental and swallowing examinations, and the care-staff assessed nutritional status, comorbid conditions and cognitive function using the Clinical Dementia Rating (CDR). RESULTS: Poisson regression analysis showed that 0-19 teeth without dentures were associated with severe cognitive impairment (CDR 3) (prevalence ratio = 2.00; 95% confidence interval: 1.13-3.55) after adjustment for sex, age, suspected swallowing dysfunction and comorbid conditions. Mediation analysis confirmed that the nutritional status as a mediator of this association (the percentage mediated effect through nutritional status was 23.1%). CONCLUSION: There is an association between dental status and cognitive impairment in elder individuals, and dentures and poor nutrition are involved in this association. However, due to the cross-sectional design of this study, there is a possibility that this association is bidirectional.

10-year trend of tooth loss and associated factors in a Japanese population-based longitudinal study.

OBJECTIVES: We examined the trend in the number of missing teeth in a Japanese community over a 10-year period and the potential associated explanatory factors. DESIGN: Prospective cohort study. SETTING: A population-based study conducted in 2007, 2012 and 2017 in Japan (Hisayama Study). PARTICIPANTS: Residents of a Japanese community aged 40-79 years undergoing dental examination in 2007 (n=2665), 2012 (n=2325) and 2017 (n=2285). OUTCOME MEASURES: The number of missing teeth, periodontal condition, dental caries experience, dental plaque index and oral health behaviours were evaluated each year. The longitudinal analysis of variation in these factors were assessed using mixed models. RESULTS: The age-adjusted and sex-adjusted mean number of missing teeth decreased with time (6.80 in 2007, 6.01 in 2012 and 4.99 in 2017). The mean clinical attachment level (CAL), prevalence of periodontitis and dental plaque index decreased over the study period, while dental caries experience slightly increased. The level of oral health behaviour increased over time. Poisson mixed models showed that changes in mean CAL and dental caries experience were positively associated with the change in the number of missing teeth over time. Linear mixed models showed that changes in dental plaque index and no regular dental visit were positively associated with changes in mean CAL. CONCLUSIONS: These findings suggest that a decreasing trend regarding the number of missing teeth in Japan might be associated with improvements in the periodontal condition due to changes in oral hygiene level and oral health behaviour.

Association between periodontitis and fibrotic progression of non-alcoholic fatty liver among Japanese adults.

AIM: Non-alcoholic fatty liver (NAFL) is known to develop into liver fibrosis, which increases the risk of liver cirrhosis and liver cancer. The association between periodontal condition and fibrotic progression of NAFL is unclear. This study aimed to clarify this longitudinal association. MATERIALS AND METHODS: Among 4812 participants aged 35-64 years undergoing annual health check-ups between 2003 and 2004, and follow-up 5 years later, 392 participants were diagnosed with NAFL. After excluding participants with liver fibrosis at baseline, 341 participants were followed up for 5 years. NAFL disease fibrosis score of ≥-1.455 was used to evaluate the probability of the presence of liver fibrosis. RESULTS: During the follow-up period, 10.6% of participants progressed to liver fibrosis. A higher clinical attachment level (CAL) tended to be associated with the incidence of liver fibrosis in the logistic regression analysis (odds ratio [OR] 1.82, 95% confidence interval [CI], 0.94-3.49, p = .074). The stratified analysis by obesity revealed a significant association with higher CAL in obese participants (OR 2.87, 95% CI, 1.23-6.69, p = .015), but not in non-obese participants. CONCLUSION: Higher CAL was associated with an increased probability of liver fibrosis in obese adults with NAFL.

Longitudinal Associations of Toothbrushing With Obesity and Hyperglycemia.

BACKGROUND: Toothbrushing is a health-related lifestyle habit and has been reported to contribute not only to oral health but also to some parameters of general health; however, little research has been conducted to understand the association of the frequency and timing of toothbrushing with the development of comprehensive metabolic abnormalities, with consideration of oral health condition. In this study, using longitudinal data, we examined this association in Japanese adults, adjusting for periodontal condition. METHODS: A 5-year longitudinal study was performed with 4,537 participants between 35 and 64 years old who underwent an annual dental examination in both 2003 and 2008. Data about toothbrushing habits and metabolic abnormalities, such as obesity, hyperglycemia, diabetes, hypertension, hypertriglyceridemia, and low levels of high-density lipoprotein-cholesterol, were analyzed using Poisson regression analysis. RESULTS: The percentage of participants with a toothbrushing frequency ≤1 time/day was 29.4%, and that for those not brushing their teeth at night was 21.4%. The incidences of obesity and hyperglycemia after 5 years were 5.5% and 28.4%, respectively. A toothbrushing frequency ≤1 time/day was associated with development of obesity (prevalence rate ratio [PRR] 1.77; 95% confidence interval [CI], 1.12-2.80), after adjusting for periodontal condition and potential risk factors. A significant association between not brushing teeth at night and hyperglycemia (PRR 1.30; 95% CI, 1.02-1.66) was observed in participants with toothbrushing frequency of 1 time/day. No association was found between toothbrushing habits and other metabolic abnormalities. CONCLUSIONS: This study suggests that toothbrushing habits are associated with the development of obesity and hyperglycemia.

Periodontal status and lung function decline in the community: the Hisayama study.

This study aimed to determine whether periodontal status is related to a decline in lung function in a general Japanese population. We followed a total of 1,650 community-dwelling individuals (≥40 years) without chronic obstructive pulmonary disease, with at least one teeth, for 3 years. Periodontal status was assessed at baseline by clinical attachment loss (CAL) and probing pocket depth (PPD) at two sites for each tooth, and the mean values were calculated for each subject. Lung function was measured at baseline and follow-up using spirometry, and longitudinal decline in forced expiratory volume in one second (FEV1) was calculated. Multivariate Poisson regression with robust error variance was used to estimate risk ratio (RR). After adjusting for potential confounders including smoking status, there was a tendency for the adjusted RR of developing rapid lung function decline (≥160 mL/3years, the highest quartile of the distribution of FEV1 declines) to increase as mean CAL levels increased (P trend = 0.039). Likewise, a positive association was observed between mean PPD levels and RR of developing rapid lung function decline (P trend = 0.047). Our findings suggest deterioration of periodontal status could be a risk factor for rapid lung function decline in the general Japanese population.

Decreased cognitive function is associated with dysphagia risk in nursing home older residents.

OBJECTIVE: To examine the association between cognitive function and dysphagia risk among Japanese nursing home residents. BACKGROUND: Reduction in cognitive function can influence the intake of food during swallowing, and may be an aggravating factor in dysphagia. METHODS: This cross-sectional study included 236 residents aged ≥60 years from eight nursing homes. Screening of dysphagia, especially aspiration risk, was conducted using the Modified Water Swallow Test, whose scores from one to three were classified as at risk of dysphagia. Cognitive function was evaluated using Mini-Mental State Examination (MMSE). Number of teeth and occlusal support were evaluated by clinical examination. The participants were stratified into dentulous and edentulous groups, because the number of teeth could influence swallowing function. The odds ratio (OR) and 95% confidence interval (CI) for dysphagia risk based on the scores of MMSE were calculated using logistic regression. Demographic characteristics, activity of daily living, comorbidities, health behaviour and occlusal support were used as covariates. RESULTS: Among the 236 participants (111 dentulous participants and 125 edentulous participants) included in our analysis, 16.9% belonged to risk of dysphagia. Dentulous participants with higher scores of MMSE tended to have significantly lower odds of dysphagia risk after adjusting for covariates (OR = 0.87, 95% CI = 0.80-0.96). Despite the lack of significant differences, edentulous participants with higher score of MMSE tended to have lower odds of dysphagia risk (OR = 0.92, 95% CI = 0.83-1.00). CONCLUSION: Decreased cognitive function may be an independent predictor of dysphagia among dentulous and edentulous adults.

Factors affecting the appetites of persons with Alzheimer's disease and mild cognitive impairment.

AIM: Appetite loss has been associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Among older people, decreased appetite can result in poor nutrition and subsequent loss of independent living. We examined the factors related to appetite loss in persons with AD and MCI to provide evidence for countermeasures to prevent appetite loss and progression of cognitive impairment. METHODS: We included 1238 older adults undergoing outpatient treatment at the Center for Comprehensive Care and Research on Memory Disorders (Medical Center for Dementia) at the National Center for Geriatrics and Gerontology in Obu, Japan. The Council on Nutrition Appetite Questionnaire, an appetite questionnaire for older people, was used to evaluate appetite. Appetite loss in persons diagnosed with AD or MCI was divided into two groups according to the Council on Nutrition Appetite Questionnaire scores, and logistic regression analysis was carried out to identify independent factors associated with appetite loss. The following variables were used to evaluate for covariates: general information, functional evaluation and medications. RESULTS: The AD and MCI groups contained 853 and 385 individuals, respectively. In both groups, depression and difficulty in maintaining attention while eating were significantly associated with poor appetite. Among persons with AD, lower vitality, more comorbidities, non-use of antidementia drugs and use of psychotropic drugs were also significantly associated with poor appetite. CONCLUSIONS: The present study recognized possible factors individually associated with appetite loss among persons with AD or MCI. Future studies are required to examine supportive strategies to treat poor appetite in these populations. Geriatr Gerontol Int 2018; 18: 1236-1243.

Tooth loss and pneumonia mortality: A cohort study of Japanese dentists.

Although associations between oral health and pneumonia have been reported in previous studies, particularly in the institutionalized elderly, few prospective studies have investigated the association between oral condition and pneumonia among community-dwelling people and whether the findings among inpatients or patients in nursing homes are applicable to the general population is still unclear. The oral bacteria propagated in the periodontal regions may drop into the lung and increase the risk of pneumonia. We, therefore, investigated the association of tooth loss with mortality from pneumonia in a cohort study of Japanese dentists. Members of the Japan Dental Association (JDA) participated in the LEMONADE (Longitudinal Evaluation of Multi-phasic, Odontological and Nutritional Associations in Dentists) Study. From 2001 to 2006, they completed a baseline questionnaire on lifestyle and health factors including the number of teeth lost (excluding third molars). We followed 19,775 participants (mean age ± standard deviation, 51.4 ± 11.7 years; 1,573 women [8.0%] and 18,202 men [92.0%]) for mortality from pneumonia (ICD-10, J12-J18). Mortality data were collected via the fraternal insurance program of the JDA. The hazard ratios (HRs) were estimated with adjustment for sex, age, body mass index, smoking status, physical activity and diabetes history. During the median follow-up period of 9.5 years, we documented 68 deaths from pneumonia. Participants who were edentulous at baseline were at significantly increased risk of mortality from pneumonia. The multivariable-adjusted HRs were 2.07 (95% confidence interval [CI], 1.09-3.95) for the edentulous and 1.60 (95% CI, 0.83-3.10) for loss of 15-27 teeth relative to loss of 0-14 teeth (trend p = 0.026). The HR per one tooth loss was also significant; 1.031 (95% CI, 1.004-1.060). In conclusion, a large number of teeth lost may indicate an increased risk of mortality from pneumonia in community-dwelling populations.

Relationship of toothbrushing to metabolic syndrome in middle-aged adults.

AIM: To examine the effect of toothbrushing on the development of metabolic syndrome (MetS), including assessment of periodontal status, in middle-aged adults. METHODS: This 5-year follow-up retrospective study was performed in 3,722 participants (2,897 males and 825 females) aged 35-64 years who underwent both medical check-ups and dental examinations. Metabolic components included obesity, elevated triglycerides, blood pressure, fasting glucose and reduced high-density lipoprotein. Toothbrushing frequency was assessed using a questionnaire. Periodontal disease was defined as having at least one site with a pocket depth of ≥4 mm. Logistic regression analysis was performed to evaluate the relationship between toothbrushing frequency at the baseline examination and the development of MetS (≥3 components). RESULTS: During follow-up, 11.1% of participants developed MetS. After adjusting for potential confounders including periodontal disease, participants with more frequent daily toothbrushing tended to have significantly lower odds of developing MetS (p for trend = .01). The risk of development of MetS was significantly lower in participants brushing teeth ≥3 times/day than in those brushing teeth ≤1 time/day (odds ratio = 0.64, 95% confidence interval = 0.45-0.92). CONCLUSIONS: Frequent daily toothbrushing was associated with lower risk of development of MetS.

Relationships of Variations in the Tongue Microbiota and Pneumonia Mortality in Nursing Home Residents.

Background: Aspiration of oral debris, containing dense oral bacteria, is a major cause of pneumonia in elderly adults. This study investigated the relationship between tongue microbiota composition and incidence of pneumonia-related deaths, in nursing home residents. Methods: The subjects were assessed for health conditions, including their tongue microbiota, at baseline. We determined tongue microbiota profiles by 16S ribosomal RNA gene sequencing and clustering approach. All subjects (n = 173) were followed prospectively for a median of 19 months to assess the incidence of all-cause death, including pneumonia-related death. We evaluated risk estimates of microbiota effects on death using multivariate Cox proportional hazards regression analysis. Results: Tongue microbiota were classified into two community types: type I was dominated by Prevotella and Veillonella species, while type II was dominated by Neisseria and Fusobacterium species. The subjects with type I microbiota exhibited a significantly greater risk of all-cause death (adjusted hazard ratio [aHR] = 3.79, 95% confidence interval [CI] = 1.38-10.39) and pneumonia-related death (aHR = 13.88, 95% CI = 1.64-117.21), than those with type II microbiota. There was no significant association between microbiota type and other-cause death. Conclusions: The tongue microbiota type was significantly associated with an increased mortality risk from pneumonia in nursing home residents.

Metallothionein MT2A A-5G Polymorphism as a Risk Factor for Chronic Kidney Disease and Diabetes: Cross-Sectional and Cohort Studies.

Metallothioneins (MTs) are proteins that protect cells from toxic agents such as heavy metal ions or reactive oxygen species. MT2A A-5G is a single nucleotide polymorphism in the promoter region of the MT2A gene, and the minor G allele results in lower transcription efficiency. We aimed to elucidate associations between MT2A A-5G and risks of 2 diseases potentially related to lowered MT expression, chronic kidney disease (CKD), and diabetes mellitus (DM), in a community-dwelling population. Study subjects were Nagoya city residents participating in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC) Daiko Study, comprised 749 men and 2,025 women, aged 39-75 years. CKD (>stage 3) and DM were defined by standard guidelines. Associations were evaluated using logistic regression models with adjustments for age, sex and potential confounders in a cross-sectional study, and verified in a 5-year longitudinal study. Odds ratios (OR [95% confidence interval]) were calculated relative to the AA genotype. Serum MT (I + II), Cd and zinc levels were also determined by genotype. The OR of the GG genotype for CKD risk was 3.98 (1.50, 10.58) in the cross-sectional study and 5.17 (1.39, 19.28) in the longitudinal study. The OR of the GA genotype for DM was 1.86 (1.26, 2.75) in the cross-sectional study and 2.03 (1.19, 3.46) in the longitudinal study. MT2A A-5G may be associated with CKD and DM risks. This polymorphism is a promising target for evaluations of CKD and DM risks with possible involvement of low-dose chronic exposure to environmental pollutants.

The effects of URAT1/SLC22A12 nonfunctional variants, R90H and W258X, on serum uric acid levels and gout/hyperuricemia progression.

Urate transporter 1 (URAT1/SLC22A12), a urate transporter gene, is a causative gene for renal hypouricemia type 1. Among several reported nonsynonymous URAT1 variants, R90H (rs121907896) and W258X (rs121907892) are frequent causative mutations for renal hypouricemia. However, no case-control study has evaluated the relationship between gout and these two variants. Additionally, the effect size of these two variants on serum uric acid (SUA) levels remains to be clarified. Here, 1,993 primary gout patients and 4,902 health examination participants (3,305 males and 1,597 females) were genotyped with R90H and W258X. These URAT1 variants were not observed in any gout cases, while 174 subjects had the URAT1 variant in 2,499 health examination participants, respectively (P = 8.3 × 10(-46)). Moreover, in 4,902 health examination participants, the URAT1 nonfunctional variants significantly reduce the risk of hyperuricemia (P = 6.7 × 10(-19); risk ratio = 0.036 in males). Males, having 1 or 2 nonfunctional variants of URAT1, show a marked decrease of 2.19 or 5.42 mg/dl SUA, respectively. Similarly, females, having 1 or 2 nonfunctional variants, also evidence a decrease of 1.08 or 3.89 mg/dl SUA, respectively. We show that URAT1 nonfunctional variants are protective genetic factors for gout/hyperuricemia, and also demonstrated the sex-dependent effect size of these URAT1 variants on SUA (P for interaction = 1.5 × 10(-12)).

No association between Helicobacter pylori infection and diabetes mellitus among a general Japanese population: a cross-sectional study.

Several case-control studies have reported that patients with diabetes mellitus (DM) had a higher prevalence of Helicobacter pylori infection than those without DM, but these findings remain equivocal. Additionally, there are few studies examining associations between East Asian CagA-positive H. pylori and DM. This cross-sectional study aimed to investigate whether H. pylori infection was a possible risk factor for DM in a general Japanese population. The study included 5165 subjects (1467 men, 3698 women) aged 35-69 years from the Daiko Study, part of the Japan Multi-Institutional Collaborative Cohort Study. A urinary anti-H. pylori antibody was used to detect H. pylori infection. The medical history of physician-diagnosed DM was confirmed by self-administered questionnaire. The odds ratios (ORs) and their 95 % confidence intervals (CIs) for DM (current and former) were calculated using unconditional logistic regression analysis, adjusting for age, sex, educational status, alcohol use, smoking status, body mass index, energy intake, and physical activity. The prevalence of DM was 4.6 % (95 % CI 3.7-5.6 %) among 1878 participants with H. pylori infection and 3.2 % (2.6-3.8 %) among 3287 without the infection (p = 0.009). The crude, age-adjusted, and multivariate-adjusted ORs for DM in those with the infection relative to those without were 1.47 (95 % CI 1.10-1.97), 1.02 (0.76-1.38), and 0.97 (0.71-1.32), respectively. We found a significantly higher DM prevalence among those with H. pylori infection than among those without. However, almost all the difference in prevalence could be explained by the older age of those infected. Our findings did not support an association between H. pylori infection and DM.

Association between brain-muscle-ARNT-like protein-2 (BMAL2) gene polymorphism and type 2 diabetes mellitus in obese Japanese individuals: A cross-sectional analysis of the Japan Multi-institutional Collaborative Cohort Study.

AIMS: Brain-muscle-Arnt-like protein-1 (BMAL1) and BMAL2 genes are essential components of the circadian clock, and are considered to be involved in glucose homeostasis. We examined whether single nucleotide polymorphisms (SNPs) of BMAL1 and BMAL2 were associated with the prevalence of type 2 diabetes (T2DM) in the general Japanese population. METHODS: We studied 2467 subjects (1232 men and 1235 women, 35-69 years old), including 105 men and 57 women with T2DM, from the participants of the Japan Multi-institutional Collaborative Cohort Study. The association between SNPs in the BMAL1 (rs11022775 and rs2290035) and BMAL2 (rs7958822) genes and T2DM were analyzed by multiple logistic regression after adjustment for potential confounders. Analysis was also performed after stratification by body mass index (≥25 kg/m(2) and <25 kg/m(2)) to investigate an interaction between genotypes and obesity. RESULTS: The A/G and A/A genotypes of BMAL2 rs7958822 showed significantly higher adjusted odds ratios (OR) for T2DM than the G/G genotype among obese men (OR=2.2, 95% confidence intervals [CI] 1.1, 4.6, P for interaction=0.0495) and obese women (OR=2.7, 95% CI 1.1, 6.7, P for interaction=0.199). There were no significant associations between BMAL1 rs11022775 or rs2290035 genotypes and T2DM. CONCLUSIONS: To the best of our knowledge, this is the first study to show the significant association between BMAL2 rs7958822 genotype and T2DM among obese subjects.

ATP-binding cassette transporter A1 (ABCA1) R219K (G1051A, rs2230806) polymorphism and serum high-density lipoprotein cholesterol levels in a large Japanese population: cross-sectional data from the Daiko Study.

Among polymorphisms in ATP-binding cassette transporter A1 (ABCA1) gene, the available evidence demonstrates that the ABCA1 R219K polymorphism (G1051A, rs2230806) K allele is associated with a higher high-density lipoprotein cholesterol (HDL- C) level and may play a protective role against coronary artery disease (CAD) risk in Asians and Caucasians. The findings from many underpowered studies from Asian countries (n=71-597), however, still remain inconsistent. The objective of this study was to overcome the limitations of previous studies in Asia and provide solid epidemiologic evidence. Subjects were participants of a cohort study, who visited the Daiko Medical Center in Nagoya, Japan. The cohort study belongs to the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). In the Daiko Study, 5,133 participants (1,458 men and 3,675 women) aged 35-69 years enrolled from 2008 through 2010 were eligible for the analyses. The ABCA1 polymorphism was genotyped by the polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method. Among all the subjects, the genotype frequencies were 23.9% (n=1,225) for RR, 49.3% (n=2,532) for RK, and 26.8% (n=1,376) for KK, which was in Hardy-Weinberg's equilibrium (P =0.36). Background characteristics did not significantly differ among the genotypes including alcohol and tobacco use. The mean ± SD of HDL-C concentration was higher in men and women with RK or KK genotype than those with RR, although the difference between these genotypes was not statistically significant in both sexes (P =0.31 in men and 0.26 in women by ANOVA). In the multiple linear regression analysis to estimate the independent effects of the R219K polymorphism on HDL-C level, however, the number of K allele was significantly correlated with an increased level of HDL-C (trend P=0.033). Those with the KK genotype showed a significantly higher HDL-C concentration compared with those with the RR genotype by a mean of 1.18 mg/dL. The R219K polymorphism of ABCA1 independently associated with serum level of HDL-C in a large Japanese population.

Common variant of ALPK1 is not associated with gout: a replication study.

Gout is one of the most kinds of common inflammatory arthritis as a consequence of hyperuricemia. Alpha-protein kinase 1 (ALPK1) gene locates in a gout-susceptibility locus on chromosome 4q21-31, and encodes ALPK1 protein which plays a pivotal role in the phosphorylation of myosin 1. In the previous genetic study of Taiwanese populations, 3 single nucleotide polymorphisms (SNPs), rs11726117, rs231247 and rs231253, in ALPK1 gene were reported to have a significant association with gout. However, no replication study has been performed to confirm this association. Therefore, we first conducted a replication study with clinically defined gout patients in a different population. Linkage disequilibrium (LD) analyzes of the 3 SNPs in ALPK1 revealed that these SNPs are in strong LD in a Japanese population. Among the 3 SNPs of ALPK1, rs11726117 (M861T) is the only missense SNP. Therefore, rs11726117 was genotyped in a Japanese population of 903 clinically defined gout cases and 1,302 controls, and was evaluated for a possible association with gout. The minor allele frequencies of rs11726117 were 0.26 and 0.25 in the case and control groups, respectively. The association analysis has not detected a significant association between rs11726117 and gout susceptibility in a Japanese population (p = 0.44). Because ABCG2, a major causative gene for gout, also locates in the gout-susceptibility locus on chromosome 4q, these findings suggest that among genes in a gout-susceptibility locus, not ALPK1 but ABCG2 could be important as a gout-susceptible gene.