title: Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication.
abstract: BACKGROUND
  Antipsychotic affinity for the histamine H1 receptor and the muscarinic M3 receptor have been associated with the side effects weight gain, and development of diabetes, respectively.
  
  
  OBJECTIVE
  We investigated polymorphisms of the histamine H1 (HRH1) and muscarinic acetylcholine receptor M3 (CHRM3) receptor genes for an association with body mass index (BMI) and glycated hemoglobin (HbA1c).
  
  
  METHODS
  We included 430 Caucasian patients with a non-affective psychotic disorder using antipsychotics for at least 3 months. Primary endpoints of the study were cross-sectionally measured BMI and HbA1c; secondary endpoints were obesity and hyperglycaemia. Two single-nucleotide polymorphisms (SNPs) in the HRH1 gene, rs346074 and rs346070, and one SNP in the CHRM3 gene, rs3738435, were genotyped. Our primary hypothesis in this study was an interaction between genotype on BMI and antipsychotic affinity for the H1 and M3 receptor.
  
  
  RESULTS
  A significant association of interaction between haplotype rs346074-rs346070 and BMI (p value 0.025) and obesity (p value 0.005) in patients using high-H1 affinity antipsychotics versus patients using low-H1 affinity antipsychotics was found. There was no association of CHRM3 gene variant rs3738435 with BMI, and we observed no association with HbA1c or hyperglycaemia in any of the variants.
  
  
  CONCLUSIONS
  This study, for the first time, demonstrates a significant association between HRH1 variants and BMI in patients with a psychotic disorder using antipsychotics. In future, genotyping of HRH1 variants may help predicting weight gain in patients using antipsychotics.
authors.affiliation: Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. j.vehof@epi.umcg.nl
authors.forename: Jelle
authors.initials: J
authors.lastname: Vehof
authors.forename: Arne J
authors.initials: AJ
authors.lastname: Risselada
authors.forename: Asmar F Y
authors.initials: AF
authors.lastname: Al Hadithy
authors.forename: Huibert
authors.initials: H
authors.lastname: Burger
authors.forename: Harold
authors.initials: H
authors.lastname: Snieder
authors.forename: Bob
authors.initials: B
authors.lastname: Wilffert
authors.forename: Johan
authors.initials: J
authors.lastname: Arends
authors.forename: Lex
authors.initials: L
authors.lastname: Wunderink
authors.forename: Henrikus
authors.initials: H
authors.lastname: Knegtering
authors.forename: Durk
authors.initials: D
authors.lastname: Wiersma
authors.forename: Dan
authors.initials: D
authors.lastname: Cohen
authors.forename: Hans
authors.initials: H
authors.lastname: Mulder
authors.forename: Richard
authors.initials: R
authors.lastname: Bruggeman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005260:Female; D014644:Genetic Variation; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000235:genetics; D043587:Receptor, Muscarinic M3 / Q000235:genetics*; D011969:Receptors, Histamine H1 / Q000235:genetics* / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D006442:Glycated Hemoglobin; D043587:Receptor, Muscarinic M3; D011969:Receptors, Histamine H1