Further exploration of the possible influence of polymorphisms in HTR2C and 5HTT on body weight

Abstract

Receptors of the 5-HT2C subtype are of importance for the influence of serotonin on food intake, and 2 single nucleotide polymorphisms in this gene ( HTR2C)—Cys23Ser ( rs6318) and −759C>T ( rs3813929)—have been reported to be associated with weight and/or antipsychotic-induced weight gain. The present study aimed to replicate these associations; in addition, the 5-HTTLPR polymorphism in the promoter region of the serotonin transporter gene ( SLC6A4) was assessed. The polymorphisms were genotyped in subjects recruited from the normal population (n = 510), and possible associations between genotype and body mass index (BMI) were assessed. The Ser23 allele was more common in underweight subjects (BMI <20) than in normal- and overweight (BMI ≥20) subjects ( P = .006). The T allele of the −759C/T polymorphism was less common in the overweight group (BMI ≥25) ( P = .007). Homozygosity for the short allele of 5-HTTLPR was more frequent in underweight subjects ( P = .015). Our results are in agreement with previous studies, suggesting polymorphisms in HTR2C to be associated with body weight, particularly in women; and they also suggest that 5-HTTLPR may influence this phenotype. Further studies on the importance of the investigated genes for eating disorders and drug-induced weight gain are warranted.