EVALUATION OF A CYS23SER MUTATION WITHIN THE HUMAN 5-HT2C RECEPTOR GENE - NO EVIDENCE FOR AN ASSOCIATION OF THE MUTANT ALLELE WITH OBESITY OR UNDERWEIGHT IN CHILDREN, ADOLESCENTS AND YOUNG-ADULTS

Serotonin is a neurotransmitter involved in a large number of psychoph ysiological processes including the regulation of mood, arousal, aggre ssion, sleep, learning, nociceptions, nerve growth and importantly, ap petitive functions. Alterations of 5-HT receptor activity have been sh own to occur in many psychiatric diseases including depression, anxiet y, eating disorders, schizophrenia etc. Hence, genetic variation in ge nes coding for serotonin receptor proteins might well be involved in t he genetic predisposition to these diseases and therefore are of great pharmacogenetic relevance. Knockout mice deficient of a functional 5- HT2C receptor have implicated a potential role of this receptor subtyp e in the serotonergic control of appetite. A Cys23Ser mutation in the human 5-HT2C receptor gene discovered recently prompted us to investig ate this mutation with regard to the development of human obesity. We have evaluated this mutation in 241 obese children and adolescents (me an BMI greater than or equal to 97th percentile), 80 normal weight chi ldren (BMI 5th - 85th percentile) and 92 underweight probands (BMI les s than or equal to 15th percentile) for a possible association with ob esity. The frequencies of the mutant allele in all three weight groups (obese subjects: 0.1597; normal weight: 0.168; underweight: 0.1575) w ere very similar. Association as well as linkage studies were negative . Therefore it is unlikely that this receptor mutation plays a direct role in the development of human obesity. (C) 1997 Elsevier Science In c.