Ryutaro Ohtsuka

FTO polymorphisms in oceanic populations

AbstractIt has been suggested that Neels “thrifty genotype” model may account for high body weights in some Oceanic populations, which presumably arose in modern times. In European populations, common variants (rs1421085-C, rs17817449-G, and rs9939609-A) in the fat mass and obesity (FTO associated) were recently found to be associated with body mass index (BMI) or obesity. In this study, we investigated the population frequencies of these variants in six Oceanic populations (Melanesians, Micronesians, and Polynesians) and tested for an association with BMI. Unlike European populations, the Oceanic populations displayed no significant association between the FTO polymorphisms and BMI. These variants were in strong linkage disequilibrium. The population frequencies ranged between 4.2 and 30.3% in the six Oceanic populations, and were similar to those in southeast and east Asian populations. Our study of the FTO polymorphisms has generated no evidence to support the thrifty genotype hypothesis for Oceanic populations.

Identification of novel functional variants of the melanocortin 1 receptor gene originated from Asians.

Human melanocortin 1 receptor (MC1R) is a seven transmembrane G-coupled protein receptor that upregulates the cAMP pathway. Several functional variants of MC1R that show an impaired ability to activate the cAMP pathway are strongly associated with fair skin and red hair in Europeans and European descendants. The sequence variations of the MC1R gene were repeatedly investigated against worldwide populations; however, there was no evidence that functional variant of MC1R exists in non-European descendants. We report the presence of novel functional variants of MC1R with Asian origins. Three novel variants of MC1R, Phe147Δ, Thr157Ile, and Pro159Thr, were identified in our screening for the sequence variations of the MC1R gene against 995 individuals from 30 Asian and Oceanian populations; there was a single case for the Pro159Thr variant allele and two instances of Phe147Δ and Thr157Ile variant alleles. Our pharmacological assay revealed that Phe147Δ, Thr157Ile, and Pro159Thr variant showed similar or more dramatically impaired activities in comparison with Arg151Cys, which is a major functional variant of MC1R in Europeans. These functional variant alleles were geographically localized in relatively high latitudes, which suggest that the adaptation to ambient UV light intensity may play an important role in shaping the geographical distribution of MC1R alleles in Asia and Oceania.

Gene Flow and Natural Selection in Oceanic Human Populations Inferred from Genome-Wide SNP Typing

It is suggested that the major prehistoric human colonizations of Oceania occurred twice, namely, about 50,000 and 4,000 years ago. The first settlers are considered as ancestors of indigenous people in New Guinea and Australia. The second settlers are Austronesian-speaking people who dispersed by voyaging in the Pacific Ocean. In this study, we performed genome-wide single-nucleotide polymorphism (SNP) typing on an indigenous Melanesian (Papuan) population, Gidra, and a Polynesian population, Tongans, by using the Affymetrix 500K assay. The SNP data were analyzed together with the data of the HapMap samples provided by Affymetrix. In agreement with previous studies, our phylogenetic analysis indicated that indigenous Melanesians are genetically closer to Asians than to Africans and European Americans. Population structure analyses revealed that the Tongan population is genetically originated from Asians at 70% and indigenous Melanesians at 30%, which thus supports the so-called Slow train model. We also applied the SNP data to genome-wide scans for positive selection by examining haplotypic variation and identified many candidates of locally selected genes. Providing a clue to understand human adaptation to environments, our approach based on evolutionary genetics must contribute to revealing unknown gene functions as well as functional differences between alleles. Conversely, this approach can also shed some light onto the invisible phenotypic differences between populations.

Anthropometry of 5–19-year-old Tongan children with special interest in the high prevalence of obesity among adolescent girls

Background: Despite much concern about adult obesity among Pacific Islanders, childhood obesity has seldom been investigated. Aim: Based on the anthropometry of Tongan children aged 5–19 years, this study aims to elucidate age and sex differences in obesity prevalence calculated from BMI and its relation to body fat estimated by skinfold thicknesses. Subjects and methods: 895 students, aged 5–19 years, in the most modernized island and a remote island, were measured for stature, body weight, circumferences at waist, hip and mid-upper arm, and skinfold thicknesses at biceps, triceps and subscapular. The prevalence of overweight and obesity was calculated using the reference data of the International Obesity Task Force (IOTF) and the Centers for Disease Control and Prevention (CDC). Results: The prevalence of obesity of Tongan adolescent girls defined by the IOTF and CDC references was 19.4% and 22.8%, respectively, being considerably higher than that of not only juvenile girls but also adolescent boys. Among adolescents, the girls’ BMI was positively correlated with fat mass whereas in boys it was not. The sex difference in adolescents was parallel to that in adults, being attributable to gender differences in daily behavioural patterns.Conclusions: Among Tongan adolescents, obesity prevalence in girls was much higher than in boys, in association with fat accumulation in the former. Résumé. Arrière plan: Malgré l’attention portée au cas de l’obésité des adultes autochtones des îles du Pacifique, l’obésité des enfants n’a que rarement été étudiée. But: Cette étude qui est fondée sur l’anthropométrie des enfants de Tonga entre 5 et 19 ans, cherche à observer les différences d’âge et de sexe dans la prévalence de l’obésité, à partir de l’IMC et de ses relations avec la graisse corporelle estimée par les plis cutanés. Sujets et méthodes: 895 élèves âgés de 5 à 19 ans pris dans l’île la plus moderne et dans une île éloignée, ont été mesurés pour la stature, le poids, les circonférence de la taille, des hanches et du bras, ainsi que pour les plis cutanés bicipital,tricipital et subscapulaire. Les prévalences du surpoids et de l’obésité ont été calculées au moyen des données de référence de « l’u2009International Obesity Task Force » (IOTF) et des Centres de Contrôle et de prévention des Maladies (CCPM). Résultats: La prévalence de l’obésité des adolescentes Tonga selon les références de l’IOTF et des CCPM est respectivement de 19,4% et de 22,8%, cest-à-dire beaucoup plus élevée que celle non seulement des filles juvéniles, mais aussi des garçons adolescents. Chez les adolescents en général, l’IMC des filles est positivement corrélé avec la masse graisseuse, tandis qu’il n’en est pas ainsi pour les garçons. Les différences liées au sexe chez les adolescents, sont parallèles à celles qui sont observées chez les adultes, elles sont attribuables aux différences d’activité quotidienne associées à chaque sexe. Conclusion: Chez les adolescents des Iles Tonga, la prévalence de l’obésité des filles est beaucoup plus élevée que celle des garçons, en association avec leur accumulation de graisse. Zusammenfassung. Hintergrund: Trotz großer Besorgnis hinsichtlich des Auftretens von Adipositas bei erwachsenen Bewohnern der Pazifischen Inseln, ist die Adipositas im Kindesalter wenig untersucht. Ziel: Auf der Basis von anthropometrischen Messungen bei 5-19-jährigen Kindern und Jugendlichen aus Tonga will diese Untersuchung Klarheit schaffen hinsichtlich von Alters- und Geschlechtsunterschieden in der Adipositasprävalenz, berechnet über den BMI in Abhängigkeit von Körperfett, geschätzt über die Hautfettfaltendicke. Probanden und Methoden: Körperhöhe, Körpergewicht, Bauch-, Hüft-, und Oberarmumfänge und Bizeps-, Trizeps- und subskapulare Hautfettfaltendicke wurden bei 895 5—19-jährigen Schülern der am stärksten modernisierten und einer entlegenen Insel gemessen. Die Prävalenz von Übergewicht und Adipositas wurde unter Verwendung von Referenzdaten der Internationalen Adipositas-Aktionsgruppe (International Obesity Task Force, IOTF) und von Zentren für Krankheitskontrolle und Prävention (Centers for Disease Control and Prevention, CDC) gerechnet. Ergebnisse: Die Adipositasprävalenz bei jugendlichen Tonganischen Mädchen, definiert über IOTF und CDC Referenzwerte, betrug 19,4%, bzw. 22,8% und war damit beträchtlich höher als die jüngerer Mädchen und die jugendlicher Knaben. Unter den Jugendlichen war der BMI von Mädchen positiv mit Fettmasse korreliert, bei Knaben aber nicht. Der Geschlechtsunterschied bei den Jugendlichen entsprach dem der Erwachsenen und ließ sich mit Geschlechtsunterschieden im Tagesablauf begründen. Zusammenfassung: Unter Tonganischen Jugendlichen war die Adipositasprävalenz bei Mädchen deutlich höher als bei Knaben und bei ersteren mit einer Fettvermehrung vergesellschaftet. Resumen. Antecedentes: A pesar de la gran preocupación por la obesidad del adulto entre los habitantes de las islas del Pacífico, raramente se ha investigado la obesidad infantil. Objetivo: Mediante datos antropométricos de los niños de Tonga de entre 5 y 19 años de edad, este estudio pretende aclarar las diferencias en edad y sexo en la prevalencia de la obesidad calculada a partir del IMC, y su relación con la grasa corporal estimada mediante el espesor de los pliegues de grasa subcutánea. Sujetos y métodos: Se midieron 895 estudiantes de entre 5 y 19 años de edad, en la isla más modernizada y en la más remota, tomando medidas de la estatura, el peso corporal, los perímetros de la cintura, cadera y brazo superior, y los pliegues de grasa subcutánea del bíceps, tríceps y subescapular. La prevalencia del sobrepeso y la obesidad se calculó utilizando los datos de referencia del International Obesity Task Force (IOTF) y de los Centros para el Control y la Prevención de enfermedades (CDC). Resultados: La prevalencia de la obesidad en las niñas adolescentes de Tonga, definida a partir de las referencias IOTF y CDC, fue de 19,4% y 22,8%, respectivamente, siendo considerablemente más alta que la de las niñas no juveniles y que la de los chicos adolescentes. Entre los adolescentes, el IMC de las chicas estaba positivamente correlacionado con la masa grasa, mientras que no lo estaba en los chicos. La diferencia sexual en los adolescentes era paralela a la de los adultos, lo que se puede atribuir a diferencias de género en los patrones del comportamiento diario. Conclusiones: Entre los adolescentes de Tonga, la prevalencia de la obesidad era mucho mayor en las chicas que en los chicos, y estaba asociada con la acumulación de grasa en las primeras.

Twenty years demographic change in sedentes and migrants of an international migrant-sending community in Tonga.

In the Kingdom of Tonga, migration to overseas developed countries has prevailed. To elucidate the effects of migration on population dynamics, an interview survey was conducted in the migrant-sending community of Kolovai, in the outer region of Tongatapu Island. All births, deaths, marriages and in- and out-migrations that took place between 1983 and 2002 were recorded for all members of the Kolovai population, consisting of persons who had lived in this community for at least a one-year period during this 20 years. The Kolovai population members, numbering 1184 (564 males and 620 females), were divided into three groups based on residence at the end of each year, i.e. Kolovai (called KK), other places in Tonga (KT) or overseas countries (KO). The KK population decreased from 774 in 1982 to 570 in 2002, owing mostly to an increase of 167 persons as the natural balance and a decrease of 324 persons as the balance of international migration. Comparison of total fertility rate (TFR) between KK and KO women revealed that the mean TFR of the former decreased from 3.460 in the earlier 10-year period (1983-1992) to 2.240 in the later 10-year period (1993-2002), while that of the latter was more than 3.5 in both 10-year periods. This difference was largely due to the decrease in the proportion married among KK women. If the current trends of international migration and fertility continue, the population of Kolovai will be reduced and its age composition will become cylinder-shaped in the near future.