Impact of HSD11B1 polymorphisms on BMI and components of the metabolic syndrome in patients receiving psychotropic treatments.
BACKGROUND
Metabolic syndrome (MetS) associated with psychiatric disorders and psychotropic treatments represents a major health issue. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme that catalyzes tissue regeneration of active cortisol from cortisone. Elevated enzymatic activity of 11β-HSD1 may lead to the development of MetS.


METHODS
We investigated the association between seven HSD11B1 gene (encoding 11β-HSD1) polymorphisms and BMI and MetS components in a psychiatric sample treated with potential weight gain-inducing psychotropic drugs (n=478). The polymorphisms that survived Bonferroni correction were analyzed in two independent psychiatric samples (nR1=168, nR2=188) and in several large population-based samples (n1=5338; n2=123 865; n3>100 000).


RESULTS
HSD11B1 rs846910-A, rs375319-A, and rs4844488-G allele carriers were found to be associated with lower BMI, waist circumference, and diastolic blood pressure compared with the reference genotype (Pcorrected<0.05). These associations were exclusively detected in women (n=257) with more than 3.1 kg/m, 7.5 cm, and 4.2 mmHg lower BMI, waist circumference, and diastolic blood pressure, respectively, in rs846910-A, rs375319-A, and rs4844488-G allele carriers compared with noncarriers (Pcorrected<0.05). Conversely, carriers of the rs846906-T allele had significantly higher waist circumference and triglycerides and lower high-density lipoprotein-cholesterol exclusively in men (Pcorrected=0.028). The rs846906-T allele was also associated with a higher risk of MetS at 3 months of follow-up (odds ratio: 3.31, 95% confidence interval: 1.53-7.17, Pcorrected=0.014). No association was observed between HSD11B1 polymorphisms and BMI and MetS components in the population-based samples.


CONCLUSIONS
Our results indicate that HSD11B1 polymorphisms may contribute toward the development of MetS in psychiatric patients treated with potential weight gain-inducing psychotropic drugs, but do not play a significant role in the general population.
aUnit of Pharmacogenetics and Clinical Psychopharmacology, Department of Psychiatry, Centre for Psychiatric Neuroscience bDepartment of Psychiatry, Centre of Psychiatric Epidemiology and Psychopathology cDepartment of Psychiatry, Service of Old Age Psychiatry dDepartment of Psychiatry, Service of General Psychiatry, Lausanne University Hospital, Prilly eLaboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne fDepartment of Medicine gInstitute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital hDepartment of Medical Genetics, University of Lausanne iSwiss Institute of Bioinformatics, Lausanne jDepartment of Mental Health and Psychiatry, University Hospital of Geneva kSchool of Pharmaceutical Sciences, University of Geneve, University of Lausanne, Geneva, Switzerland lFaculty of Biological and Environmental Science and Engineering, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
Lina
L
Quteineh
Frederik
F
Vandenberghe
Nuria
N
Saigi Morgui
Aurélie
A
Delacrétaz
Eva
E
Choong
Mehdi
M
Gholam-Rezaee
Pierre
P
Magistretti
Guido
G
Bondolfi
Armin
A
Von Gunten
Martin
M
Preisig
Enrique
E
Castelao
Peter
P
Vollenweider
Gerard
G
Waeber
Murielle
M
Bochud
Zoltán
Z
Kutalik
Philippe
P
Conus
Chin B
CB
Eap
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D001523:Mental Disorders / Q000150:complications* / Q000188:drug therapy; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009765:Obesity / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000009:adverse effects*; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics
D011619:Psychotropic Drugs; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human