Quteineh Lina, Vandenberghe Frederik, Saigi Morgui Nuria, Delacrétaz Aurélie, Choong Eva, Gholam-Rezaee Mehdi, Magistretti Pierre, Bondolfi Guido, Von Gunten Armin, Preisig Martin, Castelao Enrique, Vollenweider Peter, Waeber Gerard, Bochud Murielle, Kutalik Zoltán, Conus Philippe, Eap Chin B
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.
Pharmacogenet Genomics. 2015 May;25(5):246-58. doi: 10.1097/FPC.0000000000000131.
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.
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).
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.
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.
与精神障碍及精神药物治疗相关的代谢综合征（MetS）是一个重大的健康问题。11β-羟基类固醇脱氢酶1型（11β-HSD1）是一种催化可的松转化为活性皮质醇的组织再生酶。11β-HSD1酶活性升高可能导致代谢综合征的发生。
我们在接受可能导致体重增加的精神药物治疗的精神科样本（n = 478）中，研究了7个HSD11B1基因（编码11β-HSD1）多态性与体重指数（BMI）及代谢综合征各组分之间的关联。对经Bonferroni校正后留存的多态性，在两个独立的精神科样本（nR1 = 168，nR2 = 188）以及几个大型人群样本（n1 = 5338；n2 = 123865；n3 > 100000）中进行分析。
与参考基因型相比，发现HSD11B1 rs846910 - A、rs375319 - A和rs4844488 - G等位基因携带者的BMI、腰围和舒张压较低（校正P < 0.05）。这些关联仅在女性（n = 257）中检测到，rs846910 - A、rs375319 - A和rs4844488 - G等位基因携带者的BMI、腰围和舒张压分别比非携带者低3.1 kg/m²以上、7.5 cm和4.2 mmHg（校正P < 0.05）。相反，rs846906 - T等位基因携带者仅在男性中腰围和甘油三酯显著更高，高密度脂蛋白胆固醇显著更低（校正P = 0.028）。rs846906 - T等位基因在随访3个月时也与更高的代谢综合征风险相关（比值比：3.31，95%置信区间：1.53 - 7.17，校正P = 0.014）。在人群样本中未观察到HSD11B1多态性与BMI及代谢综合征各组分之间的关联。
我们的结果表明，HSD11B1多态性可能在接受可能导致体重增加的精神药物治疗的精神科患者代谢综合征的发生中起作用，但在一般人群中不发挥显著作用。
