TY - JOUR
T1 - A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans
AU - David, Sean P
AU - Murthy, Naga Venkatesha
AU - Rabiner, Eugenii A
AU - Munafó, Marcus R
AU - Johnstone, Elaine C
AU - Jacob, Robyn
AU - Walton, Robert T
AU - Grasby, Paul M
PY - 2005/3/9
Y1 - 2005/3/9
N2 - In humans, 5-HT1A receptors are implicated in anxiety and depressive disorders and their treatment. However, the physiological and genetic factors controlling 5-HT1A receptor expression are undetermined in health and disease. In this study, the influence of two genetic factors on 5-HT1A receptor expression in the living human brain was assessed using the 5-HT1A-selective positron emission tomography (PET) ligand [11C]WAY 100635. After the genotyping of 140 healthy volunteers to study population frequencies of known single nucleotide polymorphisms (SNPs) in the 5-HT1A receptor gene, the influence of the common SNP [(-1018) C>G] on 5-HT1A receptor expression was examined in a group of 35 healthy individuals scanned with [11C]WAY 100635. In the PET group, we also studied the influence of a common variable number tandem repeat polymorphism [short (S) and long (L) alleles] of the 5-HT transporter (5-HTT) gene on 5-HT1A receptor density. Whereas, the 5-HT1A receptor genotype did not show any significant effects on [11C]WAY 100635 binding, 5-HT1A receptor binding potential values were lower in all brain regions in subjects with 5-HTTLPR short (SS or SL) genotypes than those with long (LL) genotypes. Although the PET groups are necessarily a small sample size for a genetic association study, our results demonstrate for the first time that a functional polymorphism in the 5-HTT gene, but not the 5-HT1A receptor gene, affects 5-HT1A receptor availability in man. The results may offer a plausible physiological mechanism underlying the association between 5-HTTLPR genotype, behavioral traits, and mood states.
AB - In humans, 5-HT1A receptors are implicated in anxiety and depressive disorders and their treatment. However, the physiological and genetic factors controlling 5-HT1A receptor expression are undetermined in health and disease. In this study, the influence of two genetic factors on 5-HT1A receptor expression in the living human brain was assessed using the 5-HT1A-selective positron emission tomography (PET) ligand [11C]WAY 100635. After the genotyping of 140 healthy volunteers to study population frequencies of known single nucleotide polymorphisms (SNPs) in the 5-HT1A receptor gene, the influence of the common SNP [(-1018) C>G] on 5-HT1A receptor expression was examined in a group of 35 healthy individuals scanned with [11C]WAY 100635. In the PET group, we also studied the influence of a common variable number tandem repeat polymorphism [short (S) and long (L) alleles] of the 5-HT transporter (5-HTT) gene on 5-HT1A receptor density. Whereas, the 5-HT1A receptor genotype did not show any significant effects on [11C]WAY 100635 binding, 5-HT1A receptor binding potential values were lower in all brain regions in subjects with 5-HTTLPR short (SS or SL) genotypes than those with long (LL) genotypes. Although the PET groups are necessarily a small sample size for a genetic association study, our results demonstrate for the first time that a functional polymorphism in the 5-HTT gene, but not the 5-HT1A receptor gene, affects 5-HT1A receptor availability in man. The results may offer a plausible physiological mechanism underlying the association between 5-HTTLPR genotype, behavioral traits, and mood states.
U2 - 10.1523/JNEUROSCI.3769-04.2005
DO - 10.1523/JNEUROSCI.3769-04.2005
M3 - Article
C2 - 15758168
SN - 1529-2401
VL - 25
SP - 2586
EP - 2590
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 10
M1 - N/A
ER -