Lina Quteineh1, Frederik Vandenberghe, Nuria Saigi Morgui, Aurélie Delacrétaz, Eva Choong, Mehdi Gholam-Rezaee, Pierre Magistretti, Guido Bondolfi, Armin Von Gunten, Martin Preisig, Enrique Castelao, Peter Vollenweider, Gerard Waeber, Murielle Bochud, Zoltán Kutalik, Philippe Conus, Chin B Eap. 1. 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.
Abstract
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.
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:HSD11B1rs846910-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 psychiatricpatients treated with potential weight gain-inducing psychotropic drugs, but do not play a significant role in the general population.
Authors: Aurélie Delacrétaz; Anaïs Glatard; Céline Dubath; Mehdi Gholam-Rezaee; Jose Vicente Sanchez-Mut; Johannes Gräff; Armin von Gunten; Philippe Conus; Chin B Eap Journal: Clin Epigenetics Date: 2019-12-26 Impact factor: 6.551
Authors: Elena Barengolts; Stefan J Green; George E Chlipala; Brian T Layden; Yuval Eisenberg; Medha Priyadarshini; Lara R Dugas Journal: Microorganisms Date: 2019-09-05