Genetische Faktoren bei Adipositas

A. Hinney; C. Holzapfel

doi:10.1055/s-0037-1618794

Adipositas - Ursachen, Folgeerkrankungen, Therapie, Inhaltsverzeichnis

Adipositas - Ursachen, Folgeerkrankungen, Therapie 2012; 06(04): 236-242
DOI: 10.1055/s-0037-1618794

Übersichtsarbeit

Schattauer GmbH

Genetische Faktoren bei Adipositas

Molekular-genetische Befunde und deren BedeutungGenetic factors in obesityMolecular genetic data and their relevance

A. Hinney

¹Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters, Universitätsklinikum Essen (AöR)

,

C. Holzapfel

²Technische Universität München, Lehrstuhl für Ernährungsmedizin, Klinikum rechts der Isar

› Institutsangaben

Abstract

Zusammenfassung

Molekular-genetische Studien konnten bislang nur einen kleinen Anteil der interindividuellen Variabilität des Körpergewichts erklären, obwohl die Erblichkeit hoch ist. Bei den sehr wenigen bislang bekannten monogenen Formen der Adipositas führt der Ausfall eines einzelnen Genproduktes meist zu einer extremen Adipositas. Der größere Teil der Streubreite des Körpergewichts wird mutmaßlich durch das Zusammenspiel vieler einzelner Genvarianten erklärt, wobei jeder einzelnen Variante nur ein geringer Effekt zugeschrieben werden kann (polygene Adipositas). Mittels einer großen Meta-Analyse mit etwa 250 000 Personen europäischer Herkunft wurde eine Vielzahl von genetischen Varianten (so genannten Einzelnukleotidaustauschen) identifiziert, die für die Adipositas relevant sind. Die Effektstärken dieser Varianten auf das Körpergewicht sind zumeist klein, so dass sie insgesamt nur circa 1–2 % der Varianz des Body-Mass-Indexes (BMI) erklären. Neuere Studien beschäftigen sich mit den Wechselwirkungen von genetischen Faktoren und Umweltfaktoren (z.B. Lebensstil) und zeigen, dass einer genetischen Prädisposition z.B. mittels körperlicher Aktivität entgegengewirkt werden kann.

Es gibt momentan keine Konsensuserklärung, weshalb die identifizierten genetischen Faktoren die Erblichkeit bei komplexen Erkrankungen nicht vollständig erklären können. Auch die biologischen und vor allem klinischen Konsequenzen der identifizierten genetischen Varianten sind bislang unklar. Es bleibt weiterhin aktueller Forschungsgegenstand, die Funktionalität einzelner genetischer Bereiche zu untersuchen. Mutmaßlich werden in den nächsten Jahren einige funktionelle Varianten aufgeklärt, wodurch letztendlich ihr vermuteter therapeutischer Nutzen deutlicher warden kann.

Summary

Although the heritability of obesity is high, molecular-genetic studies explain up to now only a small part of the inter-individual variability of body weight. Monogenic obesity is very infrequent; loss of one single gene product leads to extreme obesity. The main part of the variability of body weight seems to be explained by interaction of many gene variants, whereas the effect of each single variant is small (polygenic obesity).

In a large meta-analysis of about 250,000 individuals with European descent more than 30 genetic variants (alleles at so called single nucleotide polymorphisms) were shown to be associated with obesity. The effects of these variants on body weight are small and explain in total only about 1–2% of the variance of the body mass index (BMI).

Recent studies have investigated the interaction of genetic and environmental factors (e.g. lifestyle). They have shown that a genetic predisposition can for instance be attenuated by physical activity. Up to now there is no consensus explanation, why identified genetic variants do not fully explain the heritability of complex diseases. Furthermore, the biological and clinical consequences of these genetic variants are largely unknown. It is a current research challenge, to investigate the function of such genetic variants and regions in order to evaluate the therapeutic relevance of the genetic findings.

Schlüsselwörter

Genetik - Epigenetik - Gen-Umwelt-Interaktion - polygen - monogen - Adipositas

Keywords

Genetics - epigenetics - gene-environment interaction - polygenetic - monogenetic - obesity

Volltext

Referenzen

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