Association of depressive symptoms with incident fractures: the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT).

This 5-year longitudinal study investigated the relationship between depressive symptoms and fracture risk in a large Japanese cohort. Depressive symptoms were a significant risk factor for hip fractures in women. PURPOSE: A relationship between depressive symptoms and fractures has not been clearly demonstrated. We aimed to investigate the relationship between depressive symptoms and 5-year fracture risk in the Japan Public Health Center-based Prospective Study for the Next Generation. METHODS: From 2011 to 2016, 114,092 participants were enrolled, and a follow-up survey was conducted 5 years later. We analyzed 30,552 men and 38,063 women aged 40-74 years who had no past fractures at baseline. Presence of depressive symptoms was defined as a modified 11-item Center for Epidemiological Studies Depression Scale score of 8 or higher, a history of depression, or use of antidepressants. Subjects were asked to report vertebral, upper limb, and/or hip fractures, except for traffic or work accidents, that occurred during the follow-up period. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for fracture were analyzed via logistic regression analysis to evaluate the relationship between depressive symptoms and fracture. RESULTS: Women with depressive symptoms demonstrated a high AOR for hip fractures (AOR: 2.78, 95% CI: 1.30 - 5.92); this result was consistent in post menopause women. In men, this association was not found for any age group or any type of fracture. CONCLUSIONS: Depressive symptoms in women may increase the risk of hip fractures. Further studies are required to explore this relationship in more detail.

Association of sugary drinks, carbonated beverages, vegetable and fruit juices, sweetened and black coffee, and green tea with subsequent depression: A five-year cohort study.

BACKGROUND & AIMS: Evidence on the impact of beverage consumption on depression is limited in the Asian population. Specifically, there is little information available on vegetable and fruit juices, while whole vegetables and fruits are reportedly protective against depression. Furthermore, evidence is scarce in differentiating the impacts of sweetened and black coffee. We aimed to examine the association of the consumption of total sugary drinks, carbonated beverages, vegetable and fruit juices, sweetened and black coffee, and green tea with subsequent depression in a general population sample. METHODS: We studied individuals without a history of cancer, myocardial infarction, stroke, diabetes, or depression at baseline in 2011-2016, with a five-year follow-up. We used Poisson regression models and the g-formula, thereby calculating the risk difference (RD) for depression. Multiple sensitivity analyses were conducted. Missing data were handled using random forest imputation. We also examined effect heterogeneity based on sex, age, and body mass index by analyzing the relative excess risk due to interaction and the ratio of risk ratios. RESULTS: In total, 94,873 individuals were evaluated, and 80,497 completed the five-year follow-up survey for depression. Of these, 18,172 showed depression. When comparing the high consumption group with the no consumption group, the fully adjusted RD (95% CI) was 3.6% (2.8% to 4.3%) for total sugary drinks, 3.5% (2.1% to 4.7%) for carbonated beverages, 2.3% (1.3% to 3.4%) for vegetable juice, 2.4% (1.1% to 3.6%) for 100% fruit juice, and 2.6% (1.9% to 3.5%) for sweetened coffee. In contrast, the fully adjusted RD (95% CI) was -1.7% (-2.6% to -0.7%) for black coffee. The fully adjusted RD for green tea did not reach statistical significance. The results were robust in multiple sensitivity analyses. We did not find substantial effect heterogeneity based on sex, age, and body mass index. CONCLUSIONS: Total sugary drinks, carbonated beverages, vegetable and fruit juices, and sweetened coffee may increase the risk of depression, whereas black coffee may decrease it.

Tongue pressure and maxillofacial muscle activities during swallowing in patients with mandibular prognathism.

BACKGROUND: Coordination among lip, cheek and tongue movements during swallowing in patients with mandibular prognathism remains unclear. OBJECTIVES: This study aimed to identify the temporal sequences of tongue pressure and maxillofacial muscle activities during swallowing in patients with mandibular prognathism and compared characteristics with those of healthy volunteers. METHODS: Seven patients with mandibular prognathism (mandibular prognathism group) and 25 healthy volunteers with individual normal occlusion (control group) were recruited. Tongue pressures and masseter, orbicularis oris, mentalis and supra- and infrahyoid muscle activities while swallowing gel were measured simultaneously using a sensor sheet system with five measurement points and surface electromyography, respectively. Onset time, offset time and durations of tongue pressure and muscle activities were analysed. RESULTS: In the mandibular prognathism group, tongue pressure was often produced first in more peripheral parts of the palate. Offset of tongue pressure in the posteromedian and peripheral parts of the palate and maxillofacial muscle activities except for orbicularis oris were delayed. Duration of tongue pressure in the anteromedian part of the palate was significantly shorter and durations of masseter, mentalis and suprahyoid muscle activities were significantly longer. Times to onset of orbicularis oris and suprahyoid muscle activities based on first onset of tongue pressure were significantly shorter. CONCLUSION: These results suggest that patients with mandibular prognathism may exhibit specific patterns of tongue pressure production and maxillofacial muscle activities during swallowing.

Asbestos in organochlorine insecticide powder sprinkled between pages of antiquarian books in a library in Japan.

Librarians at a university had planned to check the collection prior to the library renovations that began in 2015. They had previous knowledge of the presence of a light greyish-white powder with an unpleasant odour (hereinafter referred to as 'powder') sprinkled between the pages of antiquarian books in the library archive. The purpose of this study was to identify this powder with the help of experts from both inside and outside the university. The powder was qualitatively analysed using gas chromatography with mass spectrometry after hexane extraction. The powder was examined under a polarised light microscope and a field-emission scanning electron microscope equipped with an energy-dispersive X-ray spectrometer. Benzene hexachloride (BHC) was detected in the powder. Talc was the most abundant particle in the powder. The powder also contained 0.52 wt% asbestos, which belonged to the tremolite-actinolite series. No other types of asbestos were detected. The powder was presumed to be a bulking agent for BHC, and its major constituent was talc. This is the first report on asbestos-containing insecticides.

Investigation of orthognathic surgery indicators-combination with index of orthognathic functional treatment needs (IOFTN) and maxillofacial morphometric analysis.

PURPOSE: The aim of this retrospective study was to determine orthognathic surgery indicators for Japanese patients with jaw deformities using both Index of Orthognathic Functional Treatment Needs (IOFTN) and maxillofacial morphometric analysis. SUBJECTS AND METHODS: The subjects were 89 patients treated with orthognathic surgery and 92 patients treated with orthodontic treatment alone, and were classified as class I, II, or III according to the ANB angle. Based on the results for IOFTN and the results of cephalometric analysis, the indication criteria for orthognathic surgery were examined. RESULTS: In IOFTN analysis, none of patients in the orthognathic surgery group were classified as category 1 or 2, while 48% of the patients in the orthodontic treatment group were classified as category 4 or 5. The results of the cephalometric analysis of patients in classified categories 4 and 5 showed that the orthognathic surgery group had significantly greater lateral mandibular deviation in Class I cases, significantly more severe degree of mandibular retrusion in Class II cases, and significantly more severe degree of mandibular prognathism in Class III cases. The results of the logistic regression analysis showed that IOFTN was a common variable as an indication criterion for orthognathic surgery, and several different variables were also selected from the cephalometric measurements in each group. CONCLUSION: IOFTN is a highly sensitive and useful indicator as a criterion for orthognathic surgery. However, in the choice of treatment strategy, maxillofacial morphometric analyses and the patient's desired goal are important.

Prospective association of daily ambulatory activity with metabolic syndrome in middle-aged and older Japanese adults: the Toon Health Study.

BACKGROUND: This cohort study aimed to examine the relationship between objectively measured daily ambulatory activity (AA) variables and the onset of metabolic syndrome (MetS) in middle-aged and older Japanese individuals. METHODS: A total of 1,034 participants (women, 76.8%; mean age, 56.9 years) who were initially free from MetS, underwent objective assessment of daily AA using a uniaxial accelerometer at baseline. The number of steps, time accumulated in light-intensity AA (LIAA), moderate-to-vigorous intensity AA (MVAA), and total AA (LIAA + MVAA) were calculated. The diagnostic criteria outlined by the Japanese standards were employed to define the presence of MetS. To explore the association between AA variables and MetS onset, both multivariate logistic regression and a restricted cubic spline model were used while controlling for variables such as age, sex, education, alcohol habit, smoking habit, energy intake, and the number of MetS components present at baseline. RESULTS: Over the course of the 5-year follow-up period, 116 participants (11.2%) developed MetS. In terms of the number of steps, LIAA, and total AA, the third quartile had significantly lower multivariate adjusted odds ratios for MetS onset than the first quartile. The odds ratios (95% confidence intervals) were 0.386 (0.197-0.755), 0.527 (0.285-0.975), and 0.392 (0.206-0.745), respectively. In the spline model, an L-shaped association with MetS was observed for the number of steps (p for nonlinearity = 0.066), LIAA (p for nonlinearity = 0.034), and total AA (p for nonlinearity = 0.040). CONCLUSIONS: Among the variables related to AA, the index of daily amount AA, in particular, may be linked to the onset of MetS.

Relation between a history of glaucoma and subjective happiness: the JPHC-Next study.

OBJECTIVE: This population-based, cross-sectional study was performed to investigate the relationship between a history of glaucoma and subjective happiness. METHODS AND ANALYSIS: We conducted a cross-sectional questionnaire-based survey of 92 397 Japanese men and women aged 40-74 who participated in the Japan Public Health Center-based Prospective Study for the Next Generation study. A multivariable logistic regression model was used to estimate the ORs of glaucoma associated with subjective happiness and their two-sided 95% CIs. RESULTS: Among 40 727 men and 51 670 women, 1733 participants (635 men, 1098 women) had a history of glaucoma. The odds of unhappiness in male participants with a history of glaucoma were higher (OR 1.26; 95% CI 1.05 to 1.51) than in female participants (OR 1.05; 95% CI 0.90 to 1.23). In a subgroup analysis stratified by age, among participants with a history of glaucoma, males in the younger group (40-59 years) showed the most robust association with unhappiness (OR 1.40; 95% CI 1.04 to 1.88). CONCLUSIONS: These findings suggest that a history of glaucoma is related with subjective unhappiness, especially in men.

Pulse rate variability and health-related quality of life assessment with the Short Form-8 Japanese version in the general Japanese population.

We aimed to investigate the association between pulse rate variability (PRV) and health-related quality of life (HRQOL) in the general population. A cross-sectional study was conducted with 5908 Japanese men and women aged 30-79 years. PRV was assessed at rest using 5-min recordings of pulse waves with a photoplethysmographic signal from a fingertip sensor, and the time and frequency domains of PRV were determined. HRQOL was assessed with the Short Form-8 (SF-8) Japanese version, and poor HRQOL was defined as an SF-8 sub-scale score < 50. A test for nonlinear trends was performed with the generalized additive model with a smoothing spline adjusted for confounders. The lowest multivariable-adjusted odds ratios for poor physical component score were found in those who had second or third quartile levels of standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive difference (RMSSD), and high-frequency (HF) power and trended slightly upward in the higher levels. PRV-derived parameters were nonlinearly associated with poor physical component scores. In conclusion, reduced PRV-derived SDNN, RMSSD and HF power were associated with poor HRQOL in the domain of physical function. Higher levels of these parameters did not necessarily translate into better HRQOL.

Transscleral drainage to treat peripheral exudative hemorrhagic chorioretinopathy caused by retinal pigment epithelial hemorrhage.

Purpose: To report a case of peripheral exudative hemorrhagic chorioretinopathy with hemorrhagic retinal detachment and subretinal pigment epithelial hemorrhage treated with transscleral subretinal fluid drainage. Observations: The patient was a 70-year-old man with a 15-year history of diabetic retinopathy and age-related macular degeneration. During follow-up, he developed a sudden decrease in visual acuity in the left eye. Corrected visual acuity was 20/32 in the right eye and 20/800 in the left eye, and hemorrhagic retinal detachment and subretinal pigment epithelial hemorrhage were observed in the left eye. Pars plana vitrectomy and transscleral drainage of the subretinal hemorrhage and subretinal pigment epithelial hemorrhage were performed. We initially attempted to displace the subretinal pigment epithelial hemorrhage, but the subretinal hemorrhage was also displaced via a retinal pigment epithelial tear located in the temporal macula. The retina was completely reattached, although visual acuity in the left eye remained at 20/400. Conclusions and Importance: This report describes a surgical technique for hemorrhagic retinal detachment and subretinal pigment epithelial hemorrhage due to peripheral exudative hemorrhagic chorioretinopathy. We believe that transscleral subretinal fluid drainage without intentional retinal tear is a useful and safe method for patients with extensive hemorrhagic retinal detachment.

Acellular Extrinsic Fiber Cementum Is Invariably Present in the Superficial Layer of Apical Cementum in Mouse Molar.

The cementum is a highly mineralized tissue that covers the tooth root. The regional differences among the types of cementum, especially in the extrinsic fibers that contribute to tooth support, remain controversial. Therefore, this study used second harmonic generation imaging in conjunction with automated collagen extraction and image analysis algorithms to facilitate the quantitative examination of the fiber characteristics and the changes occurring in these fibers over time. Acellular extrinsic fiber cementum (AEFC) was invariably observed in the superficial layer of the apical cementum in mouse molars, indicating that this region of the cementum plays a crucial role in supporting the tooth. The apical AEFC exhibited continuity and fiber characteristics comparable with the cervical AEFC, suggesting a common cellular origin for their formation. The cellular intrinsic fiber cementum present in the inner layer of the apical cementum showed consistent growth in the apical direction without layering. This study highlights the dynamic nature of the cementum in mouse molars and underscores the requirement for re-examining its structure and roles. The findings of the present study elucidate the morphophysiological features of cementum and have broader implications for the maintenance of periodontal tissue health.

Multiomics analysis of cultured mouse periodontal ligament cell-derived extracellular matrix.

A comprehensive understanding of the extracellular matrix (ECM) is essential for developing biomimetic ECM scaffolds for tissue regeneration. As the periodontal ligament cell (PDLC)-derived ECM has shown potential for periodontal tissue regeneration, it is vital to gain a deeper understanding of its comprehensive profile. Although the PDLC-derived ECM exhibits extracellular environment similar to that of periodontal ligament (PDL) tissue, details of its molecular composition are lacking. Thus, using a multiomics approach, we systematically analyzed cultured mouse PDLC-derived ECM and compared it to mouse PDL tissue as a reference. Proteomic analysis revealed that, compared to PDL tissue, the cultured PDLC-derived ECM had a lower proportion of fibrillar collagens with increased levels of glycoprotein, corresponding to an immature ECM status. The gene expression signature was maintained in cultured PDLCs and was similar to that in cells from PDL tissues, with additional characteristics representative of naturally occurring progenitor cells. A combination of proteomic and transcriptomic analyses revealed that the cultured mouse PDLC-derived ECM has multiple advantages in tissue regeneration, providing an extracellular environment that closely mimics the environment in the native PDL tissue. These findings provide valuable insights for understanding PDLC-derived ECM and should contribute to the development of biomimetic ECM scaffolds for reliable periodontal tissue regeneration.

Effect of Sparc knockout on the extracellular matrix of mouse periodontal ligament cells.

The periodontal ligament (PDL) is a critical component in maintaining tooth stability. It is composed of cells and an extracellular matrix (ECM), each with unique roles in tissue function and homeostasis. Secreted protein acidic and rich in cysteine (SPARC), a calcium-binding matricellular glycoprotein, plays a crucial role in regulating ECM assembly and turnover, alongside facilitating cellular-ECM interactions. In the present study, mass spectrometry-based proteomics was used to assess the impacts of Sparc-knockout (KO) on PDL-derived cells. Results demonstrated that Sparc-KO significantly reduces ECM production and alters its composition with increased levels of type I collagen. Despite this increase in Sparc-KO, type I collagen was not likely to be effectively integrated into the fibrils due to collagen cross-linking impairment. Furthermore, the pathway and process enrichment analyses suggested that SPARC plays a protective role against ECM degradation by antagonistically interacting with cell-surface collagen receptors. These findings provide detailed insights into the multifaceted role of SPARC in ECM organization, including its impact on ECM production, collagen regulation, and interactions with various cellular compartments. A better understanding of these complex mechanisms is crucial for comprehending the causes of periodontal disease and tissue regeneration, where precise control of ECM organization is necessary.

The effect of age on the relationship between body mass index and risks of incident stroke subtypes: The JPHC study.

OBJECTIVE: The associations between body mass index (BMI) and stroke subtypes, particularly intracerebral hemorrhage, have not been consistent. Such inconsistencies may be due to differences in the age at which BMI was obtained. We examined the possible age modifications in the association between BMI and stroke risk. MATERIALS AND METHODS: We followed 88,754 participants, aged 40-69 years at baseline (1990-1994), of the Japan Public Health Center-based prospective (JPHC) study for stroke incidence. BMI was obtained using self-reported body weight and height, which were categorized using the following cut-off points: 18.5, 21, 23, 25, 27.5, and 30 kg/m2. Time-dependent Cox proportional hazards models that updated BMI and covariates using 5- and 10-year questionnaire responses were used to estimate hazard ratios and 95 % confidence intervals. The analyses were stratified by age group (40-59 and ≥60 years) and the age of the individuals was updated. RESULTS: During the median follow-up period of 19 years, we documented 4,690 strokes, including 2,781 ischemic strokes and 1,358 intracerebral hemorrhages. After adjusting for sex, age, smoking, alcohol consumption, leisure-time physical activity, history of hypertension, dyslipidemia, and diabetes mellitus, we observed a positive linear association between BMI and ischemic stroke (linear trend, p < 0.001) in both age groups (interaction p>0.05). In contrast, a curvilinear association between BMI and intracerebral hemorrhage was observed in both the middle (curvilinear trend, p=0.017) and the older group (curvilinear trend, p=0.098) (interaction p>0.05). CONCLUSION: BMI and stroke associations did not vary significantly with age, although the association may differ according to subtype.

Longitudinal Changes in Arterial Stiffness Associated with Physical Activity Intensity: The Toon Health Study.

AIMS: Several studies have revealed an association between moderate-to-vigorous physical activity (MVPA) and arterial stiffness, which is a known risk factor for cardiovascular disease. However, a few studies have considered the difference in the longitudinal effect of its intensity in a large general population. Therefore, we examined the effect of MVPA intensity on longitudinal changes in arterial stiffness. METHODS: We conducted a prospective cohort study involving 1,982 Japanese men and women. Arterial stiffness was measured using the cardio-ankle vascular index (CAVI) at baseline and 5-year follow-up. Physical activity was quantified using the Japan Arteriosclerosis Longitudinal Study Physical Activity Questionnaire and categorized into quartiles as MVPA levels. Linear mixed models were used to examine the differences at baseline and the rate of changes in CAVI associated with MVPA levels for over 5 years. RESULTS: The multivariable-adjusted mean differences in CAVI at baseline were significantly lower in the third (ß=-0.019 [95% confidence interval {CI}=-0.033 to -0.005]) and fourth (ß=-0.018 [95% CI=-0.035 to -0.001]) quartiles of the MVPA group compared with those in the lowest quartile of MVPA, and the significant effect persisted 5 years later. CONCLUSIONS: In summary, this study provides evidence to support the existence of a threshold for beneficial levels of MVPA in the prevention of arterial stiffness. Furthermore, this study suggests that exceeding this threshold may exert similar effects on arterial stiffness. These findings suggest that an optimal level of MVPA exists for preventing arterial stiffness, and exceeding this threshold may not engender additional benefits.

The association between masticatory ability and lower Timed Up & Go Test performance among community-dwelling Japanese aging men and women: The Toon Health Study.

Objectives: Few studies examined the association between deterioration of masticatory ability assessed by objective marker and physical function. Therefore, we examined the association between salivary flow rate which is one of the objective and surrogate marker of masticatory ability and lower Timed Up & Go (TUG) performance which is one of major measurement of physical function among aging Japanese. Methods: This cross-sectional study enrolled 464 Japanese aged 60-84 years old. Participants chewed tasteless and odorless gum for 5 min, calculated stimulated salivary flow rate (g/min) during all chews. The 3 m TUG was conducted, and 75th percentile value (6.8 s for men and 7.0 s for women) or higher was defined as lower TUG performance. Logistic regression analysis was used to examine the association between stimulated salivary flow rate and lower TUG performance. Results: We found that the stimulated salivary flow rate tended to be negatively associated with the TUG time. We also observed significant negative association between stimulated salivary flow rate and lower TUG performance; the multivariable-adjusted OR (95% confidence interval, CIs) of lower TUG performance for the highest quartile of stimulated salivary flow rate compared with the lowest quartile was 0.34 (0.16-0.69, P for trend = 0.02). Further adjusting for BMI, the association was attenuated but remaind significant; the OR (95% CIs) in highest quartile was 0.37 (0.18-0.76, P for trend = 0.04). Conclusions: Higher stimulated salivary flow, which means well masticatory ability, was inversely associated with lower TUG performance in the aging Japanese population.

Association between birth weight and prevalence of cardiovascular disease and other lifestyle-related diseases among Japanese population: JPHC-NEXT Study.

BACKGROUND: An association between birth weight and cardiovascular disease (CVD) in adulthood has been observed in many countries; however, only a few studies have been conducted in Asian populations. METHODS: We used data from the baseline survey (2011-2016) of the Japan Public Health Center-based Prospective Study for the Next Generation Cohort, which included 114,105 participants aged 40-74 years. Adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were calculated from the prevalence of present and past histories of CVD and other lifestyle-related diseases, including hypertension, diabetes, hyperlipidemia, and gout, by birth weight, using Poisson regression. RESULTS: The prevalence of CVD increased with lower birth weight, with the highest prevalence among those with birth weight under 1,500 grams (males 4.6%; females 1.7%) and the lowest one among those with birth weight at or over 4,000g (males 3.7%: females 0.8%). Among 88.653 participants (41,156 males and 47,497 females) with complete data on possible confounders, birth weight under 1,500g was associated with a higher prevalence of CVD (aPR 1.76 [95%CI 1.37-2.26]), hypertension (aPR 1.29 [95%CI 1.17-1.42]), and diabetes (aPR 1.53 [95%CI 1.26-1.86]) when a birth weight of 3,000-3,999 grams was used as the reference. Weaker associations were observed for birth weight of 1500-2499 grams and 2500-2999 grams, while no significant associations were observed for birth weight at or over 4000 g. The association between birth weight and the prevalence of hyperlipidemia was less profound, and no significant association was observed between birth weight and gout. CONCLUSION: Lower birth weight was associated with a higher prevalence of CVD, hypertension, and diabetes in the Japanese population.

Latent profile analysis approach to the relationship between daily ambulatory activity patterns and metabolic syndrome in middle-aged and elderly Japanese individuals: The Toon Health Study.

BACKGROUND: This cross-sectional study aimed to identify the accumulation patterns of objectively measured ambulatory activity (AA) variables in the Japanese middle-aged and elderly individuals and examine the relationship of these derivative patterns with metabolic syndrome (MetS). METHODS: A total of 1850 participants (66.1% women, mean age: 57.7 years) provided objectively assessed AA data using a uniaxial accelerometer. The number of steps, time accumulated in light-intensity AA (LIAA) and moderate-to-vigorous intensity AA (MVAA), and the ratio of MVAA to total AA (LIAA + MVAA) were calculated. Latent profile analysis was used to identify groups of participants based on their distinct AA patterns. Logistic regression models were used to assess the association of groups with MetS after adjusting for age, sex, alcohol intake, and cigarette smoking. RESULTS: Four distinct groups were identified: Group A had few steps and low levels of LIAA and MVAA; group B had a certain number of steps and recommended level of MVAA but low level of LIAA; group C had a certain number or more of steps, high level of LIAA, and recommended level of MVAA; group D had an extremely high number of steps and high levels of both LIAA and MVAA. The multivariate-adjusted odds ratio (95% CI) for MetS in groups B, C, and D relative to group A were 0.857 (0.611-1.201), 0.679 (0.500-0.922), and 0.434 (0.259-0.730), respectively. Groups C and D had significantly lower odds ratio of MetS compared to group A. CONCLUSION: AA pattern involving a certain number or greater of steps accumulated through not only MVAA but also LIAA may help reduce the risk of MetS compared to inactive AA pattern.

Positive association between serum resistin and smoking was strongest in homozygotes of the G-A haplotype at c.-420 C>G and c.-358 G>A in RETN promoter: the Toon Genome Study.

Resistin is mainly expressed in human monocytes/macrophages and is associated with insulin resistance, inflammation, and atherosclerosis. Serum resistin is strongly correlated with the G-A haplotype defined by single nucleotide polymorphisms (SNPs) c.-420 C>G (SNP-420) (rs1862513) and c.-358 G>A (SNP-358) (rs3219175) in the promoter region of the human resistin gene (RETN). Smoking is also associated with insulin resistance. We investigated the association between smoking and serum resistin and the effect of the G-A haplotype on this association. Participants were recruited under the Toon Genome Study (an observational epidemiology research in the Japanese population). Of these, 1975 subjects genotyped for both SNP-420 and SNP-358 were analyzed for serum resistin by grouping them based on smoking status and G-A haplotype status. RETN mRNA, isolated from whole blood cells, was evaluated in smokers (n = 7) and age-, sex-, and BMI-matched non-smokers (n = 7) with the G-A haplotype homozygotes. Serum resistin tended to be higher in current smokers who smoked more cigarettes per day (P for trend < 0.0001). The positive association between serum resistin and smoking was strongest in the G-A haplotype homozygotes, followed by heterozygotes and non-carriers (interaction P < 0.0001). This positive association was stronger in the G-A homozygotes than the C-G homozygotes (interaction P < 0.0001). RETN mRNA was 1.40-fold higher in smokers than non-smokers with the G-A homozygotes (P = 0.022). Therefore, the positive association between serum resistin and smoking was strongest in the G-A haplotype homozygotes defined by RETN SNP-420 and SNP-358.