Serotonin-related gene polymorphisms and central nervous system serotonin function.
Central nervous system (CNS) serotonergic function affects a wide range of biological and behavioral functions affecting health and disease. Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the serotonin transporter promoter (5HTTLPR) and monoamine oxidase A (MAOA-uVNTR) are associated with CNS serotonin turnover-indexed by cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA)-in a community sample of healthy adults. Subjects were 165 community volunteers without current medical or psychiatric illness, stratified with respect to ethnicity, gender, and socioeconomic status who underwent inpatient evaluation in the General Clinical Research Center of a university medical center. A significant ethnicity x genotype interaction (P=0.008) indicated that, compared to the long/long and long/short genotypes, the 5HTTLPR short/short genotype was associated with higher CSF 5-HIAA levels in African Americans, but with lower levels in Caucasians. A gender x genotype interaction (P=0.04) indicated that 5HTTLPR short/short genotype was associated with higher 5-HIAA levels in women but with lower levels in men. MAOA-uVNTR 3.5 and 4 repeat alleles were associated with higher 5-HIAA (P=0.03) levels in men, but were unrelated to 5-HIAA levels in women. These findings suggest that effects of serotonin-related gene polymorphisms on CNS serotonergic function vary as a function of both ethnicity and gender. Further research will be required to determine the mechanism(s) underlying these differential effects. In the meanwhile, both ethnicity and gender should be taken into account in research evaluating effects of these and related polymorphisms on CNS serotonergic function, as well as the broad range of biological and behavioral functions that are regulated by CNS serotonergic function.
Williams
Redford B
RB
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 3926, Durham, NC 27710, USA. redfordw@acpub.duke.edu
Marchuk
Douglas A
DA
Gadde
Kishore M
KM
Barefoot
John C
JC
Grichnik
Katherine
K
Helms
Michael J
MJ
Kuhn
Cynthia M
CM
Lewis
James G
JG
Schanberg
Saul M
SM
Stafford-Smith
Mark
M
Suarez
Edward C
EC
Clary
Greg L
GL
Svenson
Ingrid K
IK
Siegler
Ilene C
IC
D000328:Adult; D000704:Analysis of Variance; D002352:Carrier Proteins / Q000235:genetics; D002490:Central Nervous System / Q000378:metabolism*; D005006:Ethnicity / Q000523:psychology / Q000706:statistics & numerical data*; D005260:Female; D005838:Genotype; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic / Q000235:genetics*; D012701:Serotonin / Q000235:genetics* / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D012737:Sex Factors; D012959:Socioeconomic Factors
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D008995:Monoamine Oxidase