Okinawa Population Research Articles

Analyses of the association between Helicobacter pylori antibody titre and pathogenicity before and after eradication: results of the Kyushu and Okinawa population study, a retrospective observational cohort study

ObjectivesTo assess the utility of Helicobacter pylori antibody testing, we evaluated the correlation between the H. pylori antibody titre and H. pylori-associated pathogenicity and the changes in antibody titre after...

Exceptional longevity in Okinawa: Demographic trends since 1975.

Demographers have studied the Japanese mortality pattern since Japan became the most longevous population worldwide, half a century ago. Nutrition and lifestyle were considered by epidemiologists, gerontologists and other scientists as the most important reasons explaining the Japanese superiority. In Okinawa, the mortality pattern is even more exceptional, but few demographers have pointed out this exception. Other scientists proposed different explanations - for example some genetic characteristics, less salt and more animal protein in the food, a mild climate, a higher level of activity, a better consideration of the oldest in the population and, globally speaking, a more traditional lifestyle. At the end of the 1980s, lower improvements of mortality among young adults were identified in Okinawa. In 2002, Okinawa fell from the 4th to the 26th place in the ranking of the 47 Japanese prefectures by male life expectancy. This has been considered by the population of Okinawa as a 'shock'. Our in-depth analysis of available life tables and associated mortality rates proves that the population of Okinawa is divided into two groups of generations: those born before World War II and those born after. The older generations clearly experience a highly favourable mortality pattern, whereas the younger generations show mortality levels that are definitively higher compared to mainland Japan. This contribution considers which factors may explain such a situation, including the plausible invalidation of the age of some oldest in the population. We plea for in-depth demographic age validation that will enhance all scientific findings so far and boost the exceptional longevity in Okinawa.

Genetic relationships among populations of the small Indian mongoose (Urva auropunctata) introduced in Japan

The small Indian mongoose, Urva auropunctata, is one of the most notorious invasive species in the world. In Japan, the mongoose was introduced to Amami, Kyushu (Kiire region), and Okinawa Islands. Currently, an eradication program for the Amami population is proving successful. To prevent reinvasion and conserve biodiversity, it would be advantageous to investigate the origin and dispersal history of introduced mongoose populations in Japan. We determined the mitochondrial genome of a mongoose from the Okinawa population and confirmed that the systematic status of the mongoose is Urva auropunctata. We also found two haplotypes of cytochrome b in the Amami population, one of which is common among the Okinawa, Amami, and Kiire populations. Based on our microsatellite analysis, the three populations were genetically different from each other. Furthermore, with a low pairwise FST value, the Kiire population was closer to the Okinawa than the Amami population. Our results suggest that the Okinawa population could be the source of the Amami and Kiire populations. These results align with historical records of mongoose in Japan and clarify its genetic status. Our results should aid the prediction of the pathway through which a new invasion will likely occur.

Healthy Eating in Population Models of Nutrition: Asian Diet Style Summary

The population of Japan and Okinawa is known for the longest life expectancy, which many researchers rightly associate with the nature of nutrition existing in these territories. The Japanese diet and Okinawan diet, along with other traditional diets, are real examples of historically established sustainable patterns of healthy eating. Asian eating styles have marked differences from European eating patterns, not only in differences in food sources, but also in eating habits. The article presents the historical, climatic and cultural features of these diets; the issues of food composition, energy and nutritional value of these models of nutrition are considered in detail with an analysis of the differences existing between them; highlights the benefits of products grown mainly in Japan, which are ration-forming for the population of this country; as well as the results of scientific studies on the protective effect of the Japanese and Okinawan diets on human health and disease prevention.

Relationship between the cholesterol and triglyceride content of lipoprotein subclasses and carotid intima-media thickness: Results from the Kyushu and Okinawa Population Study (KOPS)

Background and Aims : The association between 20 lipoprotein cholesterol and triglycerides subclasses and carotid intimal medial thickness (cIMT) progression has not been evaluated fully. Our goal was to assess which lipoprotein subclasses were associated with max cIMT levels.

Population Genetic Structure of Little Tern (Sternula albifrons) in Japan Inferred from Nucleotide Sequence Diversities of the Mitochondrial DNA Control Region

Little Tern Sternula albifrons sinensis was been categorized as Endangered Class II by the 2020 Ministry of the Environment's Red List in Japan. For an effective conservation program for the taxon, the unit of conservation needs to be understood. In this study, we investigated genetic and morphological diversity as a clue to clarify the units to be protected. Blood samples were collected from 47 individuals in four different breeding sites in Japan (Tokyo, Chiba, Fukuoka, Okinawa). The nucleotide sequences of the control region of mitochondrial DNA were used to analyze their genetic diversity and structure. Basic morphological features were also compared. Nucleic acid base substitution, deletion, or insertion were identified at 30 sites of the 1029-bp sequence alignment of the control region, leading to identification of 30 different haplotypes. Genetic diversity was high in the four breeding populations, and haplotype frequencies showed no indication that specific genotypes were present at extreme frequencies. This suggests that the population of Little Tern nesting in Japan has been maintained without recent bottleneck events. The haplotype network formed two major haplotype groups from the 30 haplotypes. Haplotypes of one group were abundant in the Tokyo, Chiba, and Fukuoka populations. In contrast, those of the other group were frequent in the Okinawa population. Pairwise haplotype analysis between populations also revealed that the genetic variations at Okinawa differ from those of the remaining three populations. Furthermore, the Okinawa population showed different morphological characteristics compared to the Tokyo/Chiba populations. These results collectively suggest that the population of Little Terns in Japan is divided into at least two different populations.

Obesity and Voiding Parameters in a Community-Based Population of Okinawa, Japan: Kumejima Digital Health Project (KDHP).

(1) Background: Evidence has accumulated regarding the etiology of lower urinary tract symptoms associated with obesity and metabolic syndrome. Therefore, the present study aimed to identify which subjectively and objectively measured voiding parameters were associated with obesity in a community-based population. (2) Methods: Voiding parameters on a self-administered questionnaire and a digital self-health monitoring system for urine excretion (s-HMSU) were compared between participants with and without obesity, defined as a body mass index ≥ 25 kg/m2 (n = 30 and 29, respectively), from a community in Okinawa, Japan. Logistic regression analysis was employed to calculate the odds ratios of abnormalities in voiding parameters for the obese group, with the non-obese group serving as a reference. (3) Results: The obese group had odds ratios of 5.17 (95% confidence interval: 1.33–20.0) for shortened hours of undisturbed sleep (<302 min) by s-HMSU and 7.65 (1.88–31.1) for nighttime urinary frequency by a questionnaire after adjusting for age and sex. In addition, the obese group had an adjusted odds ratio of 2.27 (0.76–6.78) for decreased maximum bladder capacity (<212 mL) by s-HMSU. (4) Conclusion: the results of the present study suggest that nocturia and shortened hours of undisturbed sleep are signs of obesity.

Kyushu and Okinawa Population Study (KOPS): a large prospective cohort study in Japan

PurposeThe Kyushu and Okinawa Population Study (KOPS) was established to investigate gene–environmental interactions in non-communicable diseases in Japan. Besides collecting blood samples and anthropometric measurements, we also obtained medical histories,...

Abstract 9167: Relationship Between Dietary Vitamin D Intake, Obesity, and Twenty Lipoprotein Subclasses: Results from the Kyushu and Okinawa Population Study

Introduction: The correlation between serum vitamin D deficiency, obesity, and various diseases has been reported, however, there were few investigations on the role of dietary vitamin D intake on obesity and dyslipidemia. Objective: To examine whether dietary vitamin D intake affects obesity and dyslipidemia. Methods: Dietary vitamin D intake amounts calculated using obtained data of food frequency questionnaire and 20 lipoprotein cholesterol and triglycerides subclasses using gel permeation high performance liquid chromatography were analyzed in 945 men and women (mean age 58.3 years, free of thyroid or chronic liver diseases and off osteoporosis, cholesterol lowering, or adrenocorticosteroid medications). Univariate and multivariate regression, and partial correlation analyses were performed to examine the associations between dietary vitamin D intake, obesity, and lipoprotein subclasses. Results: Dietary vitamin D intake had a significant negative association with body mass index in both post- and pre-menopausal women groups ( r = -0.1053 and -0.1761, P = 0.02 and 0.04, respectively). Regarding 20 lipoprotein subclasses, dietary vitamin D intake were negatively associated with very low-density lipoprotein-3 cholesterol in premenopausal women ( r = -0.2099, P =0.02) and positively associated with total high-density lipoprotein (HDL) cholesterol in men ( r = 0.1159, P = 0.04). In addition, dietary vitamin D intake also showed a marginally positive correlation with total HDL cholesterol in premenopausal women ( r = 0.1323, P = 0.13). Those association were also found in the frequency of fish intake, a major source of vitamin D in Japan. Conclusions: Our results indicate that proactive dietary vitamin D intake may help prevent or eliminate obesity and dyslipidemia.

Abstract 9165: Relationship Between the Cholesterol and Triglyceride Content of Lipoprotein Subclasses and Carotid Imtima-Media Thickness: Results from the Kyushu and Okinawa Population Study

Introduction: The association between 20 lipoprotein cholesterol and triglycerides subclasses and carotid intimal medial thickness (cIMT) progression has not been evaluated fully. Objective: Our goal was to assess which lipoprotein subclasses were associated with max cIMT levels. Methods: Levels of cIMT and 20 lipoprotein cholesterol and triglycerides subclasses using gel permeation high-performance liquid chromatography (GP-HPLC) were analyzed in 864 men and women (mean age 57 years, free of chronic liver or kidney diseases and off cholesterol-lowering, hormone replacement, or adrenocorticosteroid medications). Univariate and multivariate regression analyses were performed to examine the relationships between lipoprotein subclasses and max cIMT levels. Results: Max cIMT levels were 0.90 mm in women and 0.97 mm in men. After adjustment for age, gender, systolic blood pressure, smoking habits, diabetes, and hypertension treatment, elevated low-density lipoprotein cholesterol-2 and -3 were associated with higher max cIMT levels in both women and men. Decreased high-density lipoprotein cholesterol-7 were associated with higher max cIMT levels only in women (all P for trend &lt; 0.05). However, no associations were found between any triglyceride subclasses and max cIMT levels. Conclusions: Our data indicate that elevated smaller LDL cholesterol levels separated by GP-HPLC were significantly associated with max cIMT in both men and women. Our results support the concept that small dense LDL cholesterol is the most atherogenic lipoprotein parameter.

Development and characterization of microsatellite markers in the small Indian mongoose (Urva auropunctata).

The small Indian mongoose (Urva auropunctata) is one of the world's worst invasive alien species and eradication programs are ongoing worldwide. The development of individual and sex identification markers will improve their management. We searched for novel mongoose microsatellite markers using genome-wide screening and identified 115,265 tetra-nucleotide repeat loci. Of 96 loci tested, 17 were genotyped in 28 mongooses from the Okinawa population. The genetic diversity analysis showed that the average expected and observed heterozygosity and number of alleles were 0.55, 0.56, and 2.94, respectively. Of 17 loci, one deviated from Hardy-Weinberg equilibrium and six loci pairs were likely linked to each other. However, we succeed in identifying all individuals using all of the microsatellite loci. The novel sex identification markers worked successfully in a test using sex known samples. Our novel microsatellite and sex identification markers should be useful in studies of individual identification and population genetics of the mongoose.

Relationship between dietary vitamin D intake, obesity, and twenty lipoprotein subclasses: Results from the Kyushu and Okinawa Population Study (KOPS)

Background and Aims: The correlation between serum vitamin D deficiency, obesity, and various diseases has been reported, however, there were few investigations on the role of dietary vitamin D intake on obesity and dyslipidemia.

Abstract P493: Small Dense Low-density Lipoprotein Cholesterol and Carotid Intimal Medial Thickness Progression

Introduction: Carotid intimal medical thickness (cIMT) is associated with cardiovascular disease (CVD). The association between atherogenic lipoproteins including small dense low-density lipoprotein cholesterol (sdLDL-C) and carotid intimal medial thickness (cIMT) progression has not been fully evaluated in a prospective cohort study. Hypothesis: We assessed the hypothesis that sdLDL-C is the most atherogenic lipoproteins with regard to cIMT progression. Methods: Kyushu and Okinawa Population Study (KOPS) is a community-based, prospective, and observational study in Japan which has been underway since 2004 and a total of 18,762 participants have been enrolled. For this study, we included 2,030 male and female participants (median age 59 years at baseline) who were free of CVD and off cholesterol lowering medication, and had cIMT measured at both baseline and after 5 years follow-up survey. Using plasma samples obtained from those subjects after overnight fast, we measured total cholesterol, direct low-density lipoprotein cholesterol (LDL-C), sdLDL-C, LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides, Lp(a), adiponectin and high sensitivity C reactive protein (hs CRP). Their cIMT levels were measured by B-mode ultrasonography with a 10 MHz probe at far walls of their both right and left common carotid arteries. Results: Median cIMT at baseline was 0.63 mm and median 5 year progression was 0.18 mm. After adjustment for standard CVD risk factor including age, gender, systolic blood pressure, total cholesterol, HDL-C, smoking, diabetes, and hypertension treatment, only LDL-C, sdLDL-C, and the sdLDL-C/LDL-C ratio were associated with cIMT progression. Even in subjects with direct LDL-C &lt; 100 mg/dL, considered to be at low CVD risk, elevated sdLDL-C were associated with cIMT progression ( P for trend = 0.009) in a model with established CVD risk factors, although the sdLDL-C/LDL-C ratio did not. Conclusions: In conclusion, both sdLDL-C and direct LDL-C are significantly associated with cIMT progression. Moreover sdLDL-C has stronger relationship with cIMT progression than does LDL-C; therefore, measurement of sdLDL-C may allow for the formulation of optimal therapy to cIMT progression.

Lifestyle modifications as therapy for medication refractory post-traumatic headache (PTHA) in the military population of Okinawa

ObjectiveOur aim was 1) to reduce disability, as characterized by headache frequency, duration and severity in patients with post-traumatic headache (PTHA), 2) to reduce the number of medical boards and work limitations in patients with post traumatic headache, and 3) to reduce use of medical resources and clinic visits related to headache or migraine.BackgroundModifiable risk factors for PTHA include stressful life event, sleep disturbances, and medication overuse. Cognitive-behavioral strategies, biofeedback, and relaxation therapy may have an important role in treatment and preventing progression to chronic post-traumatic headache (CPTHA). There is limited literature and a known practice gap for implementation of these techniques.Design/methodsAn IRB approved project focused on patients who were seen for PTHA and CPTHA. 1) Intervention consisted of lifestyle teaching, cognitive-behavioral therapy and biofeedback, supplemented by decreasing polypharmacy. 2) Patients were followed for 2 years and a retrospective review was conducted for 2 years prior to presentation. 3) Outcome measures included reduction in migraine intensity or frequency, improved quality of life, duty status, and decreased utilization of clinic visits.ResultsOver the course of one year, 221 patients were treated for migraines in the Naval Okinawa Neurology Clinic. Of these, 22 active duty service members and 3 Dependents suffered a mild TBI prior to onset. After intervention, there was a 36% decrease in PTHA frequency, 56% decrease in headache severity and 60% of patients had improved quality of life as compared to the 2 years prior to intervention. Twenty-four percent had reduction in polypharmacy. Appointment frequency for migraine decreased from an average of 6.8 to 2.6 per year.ConclusionsAn implemented program geared towards reducing polypharmacy was shown to improve safety, quality of life and reduce hospitalizations from the burden of migraines. Our systematic approach resulted in quality of life improvements and decreased use of medical resources.Trial registrationAuthors received the approval of NAVMED West, Okinawa Naval Hospital Institutional Review Board on January 13th, 2016. QI.2016.0021.

Using Botox, biofeedback and lifestyle modifications as therapy for medication refractory post-traumatic headache (PTHA) in the military population of Okinawa. (P6.295)

Using Botox, biofeedback and lifestyle modifications as therapy for medication refractory post-traumatic headache (PTHA) in the military population of Okinawa. (P6.295)

Association of the Serum Endostatin Level, Renal Function, and Carotid Atherosclerosis of Healthy Residents of Japan: Results from the Kyushu and Okinawa Population Study (KOPS).

Aim: To analyze associations among the serum endostatin level, renal function, and carotid atherosclerosis of healthy residents of Japan.Methods: Among 1,057 Japanese residents who attended free public physical examinations between 2010 and 2011, we evaluated the data of 648 healthy residents (200 men and 448 women, age 24 to 84 years) for whom the serum endostatin level and common carotid intima-media thickness (IMT) were measured. Renal function was assessed by estimated glomerular filtration rate (eGFR). Multiple linear regression analysis was done to determine the association of eGFR and serum endostatin level after adjustment for known covariates. Mediation analysis was done using Baron and Kenny's regression approach.Results: The median endostatin level was 63.7 ng/mL (interquartile range: 49.7–93.2). The mean eGFR was 78.4 ± 14.8 mL/min/1.73m2. Univariate analysis showed that age (r = −0.37, P < 0.01), non current smoking (85.8 ± 13.0 vs. 77.5 ± 14.8 mL/min/1.73 m2, P < 0.01), hemoglobin A1c (r = −0.08, P = 0.05), low-density lipoprotein-cholesterol (r = −0.13, P < 0.01), uric acid (r = −0.15, P < 0.01), carotid IMT (r = −0.11, P < 0.01), and log-transformed endostatin (r = −0.36, P < 0.01) were significantly associated with eGFR. In multiple linear regression analysis, log-transformed endostatin was significantly associated with eGFR (beta = −0.24, P < 0.01). While, carotid IMT was no longer significant. Mediation analysis showed serum endostatin level to be a mediator in the association between carotid IMT and eGFR.Conclusions: The association between carotid IMT and eGFR is mediated by the serum endostatin level of healthy individuals.

Correlation between Thyroid Stimulating Hormone and Renal Function in Euthyroid Residents of Japan: Results from the Kyushu and Okinawa Population Study (KOPS).

Aim: The present large-scale Japanese population study was performed to evaluate the relation between the serum thyroid stimulating hormone (TSH) level and renal function.Methods: Out of 1,374 residents who participated in a free public physical examination between 2010 and 2011, we evaluated the data of 888 participants for whom the serum TSH level and estimated glomerular filtration rate (eGFR) were successfully measured. The participants were categorized into three groups based on TSH levels (normal TSH, ≤ 2.4; high-normal TSH, 2.5–4.4; and subclinical hypothyroid, ≥ 4.5 µIU/mL). Multiple linear regression analysis adjusted for cardiovascular risk factors was performed to determine the relationship between serum TSH level and renal function.Results: The mean ± SD TSH level was 2.0 ± 1.4 µIU/mL, and 75.9% (n = 674) of the participants had normal, 17.9% (n = 159) had high-normal, and 6.2% (n = 55) had subclinical hypothyroid TSH levels. The mean eGFR significantly decreased with increased TSH levels (normal TSH, 79.3 ± 14.1; high-normal TSH, 77.4 ± 13.0; and subclinical hypothyroid, 72.3 ± 12.2 mL/min/1.73 m2: P for trend < 0.01). Multiple linear regression analysis extracted log-transformed TSH level as an independent factor correlated with eGFR in the high-normal TSH group (beta = −0.18, P = 0.02).Conclusions: Our findings demonstrated a significant correlation between serum TSH levels and eGFR in high-normal TSH participants. In healthy individuals, high-normal TSH levels indicate increased the risk of chronic kidney disease.

Cardiovascular disease prevalence and insulin resistance in the Kyushu–Okinawa Population Study and the Framingham Offspring Study

Age-adjusted cardiovascular disease (CVD) prevalence rates are significantly lower in Japan than in the United States. Our aim was to compare CVD risk in participants in Fukuoka and Framingham. We measured glucose, insulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), small dense LDL-C, and triglycerides in men and women from Fukuoka (n=1108), and age (median, 53years) and gender-matched subjects from Framingham (n=1101). Blood pressure, body mass index, use of medications, and history of CVD were also assessed. CVD prevalence rates were more than 6-fold higher in Framingham men and women than their Fukuoka counterparts (P<.001). Median body mass index, LDL-C, insulin levels, and insulin resistance assessment in Fukuoka men and women were significantly (P<.01) lower than in Framingham; however, diabetes prevalence in Fukuoka men was significantly (P<.01) higher than in Framingham men, whereas female rates were similar, as were levels of systolic blood pressure. High-density lipoprotein cholesterol and surprisingly small dense LDL-C levels were significantly (P<.001) higher in Fukuoka than in Framingham. Standard risk factors do not account for the large differences in CVD prevalence rates between the 2 populations, and population differences in insulin resistance may explain some of these differences. Our data are consistent with the concept that the CVD prevalence rate in a Japanese population is much lower than those observed in the United States, and that these differences cannot be explained by standard CVD risk factors, but may relate to marked population differences in insulin resistance.

The Relation between Serum Endostatin Level and Carotid Atherosclerosis in Healthy Residents of Japan: Results from the Kyushu and Okinawa Population Study (KOPS).

Aim: To examine the association between the serum endostatin levels and subclinical atherosclerosis independent of traditional risk factors in a healthy Japanese population.Methods: Among 1,057 residents who attended free public physical examinations between 2010 and 2011, we evaluated the data of 648 healthy residents for whom the serum endostatin level and common carotid intima-media thickness (IMT) were successfully measured.Results: The median endostatin level was 63.7 ng/mL (interquartile ranges: 49.7–93.2 ng/mL), and the mean carotid IMT was 0.68 ± 0.12 mm. Residents with above median endostatin had significantly higher carotid IMT than did those with below median endostatin (0.71 ± 0.14 vs. 0.65 ± 0.09 mm, P < 0.001). Multiple linear regression analysis demonstrated that increased serum endostatin is significantly associated with carotid IMT (above vs. below median endostatin level; beta = 0.11, P = 0.03), independent of the known covariates of age, sex, body mass index, drinking and smoking status, systolic blood pressure, diastolic blood pressure, hemoglobin A1c, low density lipoprotein cholesterol, estimated glomerular filtration rate, and log-transformed high sensitive C-reactive protein.Conclusions: A higher serum endostatin level reflected subclinical atherosclerosis in this Japanese population.

Cold War Geopolitics of Population and Reproduction in Okinawa Under US Military Occupation, 1945–1972

This article explores the Cold War geopolitics of population and reproduction in Okinawa under US military occupation from 1945 to 1972. Okinawa has been hailed as a “reproductive paradise,” owing to having the highest birth rate in Japan. However, its high birth rate reflects the Cold War history of US military occupation or, more specifically, the history of reproduction and the marginalization of the population in Japan. In postwar Okinawa, where the Eugenic Protection Law (EPL) was not implemented, the use of legalized abortion and contraceptive methods was restricted until the reversion to Japanese administration. The US Civil Administration of the Ryukyu Islands (USCAR) put forward emigration as a solution to Okinawa's population pressures and refused to enact the EPL, although the Government of the Ryukyu Islands (GRI) sought to implement the legislation. This article reveals that Cold War geopolitics placed Okinawa between national and international trends of population policy and family planning programs by highlighting the following three points: the GRI's awareness of Okinawa's population problem and enactment of the EPL, USCAR's choice in promoting emigration and “rescission” of the EPL, and a family planning campaign without state initiative in Okinawa under US military occupation.