Table of Contents:
Adipositas represents a serious health problem in the
current company. Investigations of the ?nationally center for Health
Statistics? between the years 1960-94 show that the share in overweight
persons in the USA in this period steadily increased. Next to an increased
food availability and a removal of the individual physical activity, genetic
factors are responsible for the development of an Adipositas. Adoption
studies and twin studies show this impressively. Formal gene tables
studies belay the genetic contribution to the phänotypic Varianz of the
body weight. Moreover the different mouse models brought new recognitions .
The Hormone Leptin that is produced by fat cells was identified 1994 and
confirmed the thesis of a hormone feed-back mechanism and a central control of
the body-weight regulation system. Also in humans relevant mutations in the
Leptin gene could be identified in single extremely adipösen persons.
Other hormones produced in the ZNS interact with this rule circle
and are therefore most likely participant of the body-weight regulation system.
The Melanocortin-4-Rezeptor plays herewith an important role.
Animal models and studies with humans places that specific mutations of the
MC4-Rezeptors are korrelated with obesity. The Proopiomelanocortin gene (POMC)
examined here is the matrix for the alpha MSH which is the natural Liganden of
the MC4-Rezeptors. Additional to alpha MSH, ACTH ,beta and gamma Lipotropin,
beta and gamma MSH, beta Endorphin and the 16-K-Fragment are produced by the
POMC gene code. Linkage analyses of threefold different cohort with different
ethical origins showed a correlation of plasma-Leptin-levels and the area of
the chromosome 2p in which the POMC gene lies. Krude et al. identified 1998
mutations in the POMC gene of two children with pigmentation interferences ACTH
deficiency and extreme Adipositas .
In this work by means of molekulargenetischer methods
(Polymerase-Chain-Reaktion, Single-strand-Conformation-Analysis) i did a
Mutationsscreen of the POMC gene at a group 96 extremely obese children.
Eight different variants were found by means of
Single-strand-Conformation-Analysis and were identified by Sequencing:
a 9-bp- insertion(AGC-AGC-GGC) as well as a
18-bp- insertion(AGC-AGC-GGC-AGC-AGC-GGC) between position 6997/6998 of the
sequence after Takahashi in the area of the 16-K-Fragments,
a 6-basenpaar insertion(GGG-CCC) between position 7304/7305 of the sequence
after Takahashi in the area coding for the gamma Lipotropin, two point
variants (Guanin to Thymin onOf which one to a chain discontinuance leads
(Nonsensemutation), and five bases couple exchanges with which the original
amino acid sequence does not change. Assoziationsstudies to these variants in
a controll-group of 60 underweight student were negative.
Therefore variants in the POMC gene in the studies group examined here have
no general influence on the Phänotyp Adipositas.