title: The major circadian pacemaker ARNT-like protein-1 (BMAL1) is associated with susceptibility to gestational diabetes mellitus.
abstract: OBJECTIVE
  Recently a relationship between circadian clock function and the risk for type 2 diabetes (T2D) has been shown. BMAL1 is a key component of the mammalian molecular clock. Two SNPs in the BMAL1 gene have been identified to confer T2D susceptibility. In the present study we investigated for the first time the association between the BMAL1 gene and the risk for GDM, in a Greek population.
  
  
  METHODS
  We studied 185 women with GDM and 161 non-diabetic controls for BMAL1 polymorphisms. For BMAL1 mRNA expression, peripheral leukocytes were harvested from 20 GDM and 20 control women, harboring different genotypes for the tested polymorphisms, using real-time quantitative PCR.
  
  
  RESULTS
  The minor allele (A) of the BMAL1 rs7950226 (G>A) polymorphism was found to be significantly associated with an increased risk of GDM (P=0.025). Analysis of the second BMAL1 rs11022775 (T>C) polymorphism, showed that the C-allele frequency was strongly increased in women with GDM (P=4.455e-06). The CC genotype was also significantly overrepresented in GDM vs. controls (P=0.00001). Additionally, the rs7950226G/rs11022775C and rs7950226A/rs11022775C haplotypes were also found to be associated with increased susceptibility to GDM. Furthermore, the expression levels of BMAL1 mRNA were significantly lower in GDM patients than in controls.
  
  
  CONCLUSIONS
  These data suggest that the impairment of the BMAL1 clock gene expression is closely associated with GDM susceptibility.
authors.affiliation: First Department of Obstetrics and Gynecology, University of Athens School of Medicine, Athens, Greece. kpappa@med.uoa.gr
authors.forename: Kalliopi I
authors.initials: KI
authors.lastname: Pappa
authors.forename: Maria
authors.initials: M
authors.lastname: Gazouli
authors.forename: Eleni
authors.initials: E
authors.lastname: Anastasiou
authors.forename: Zoe
authors.initials: Z
authors.lastname: Iliodromiti
authors.forename: Aristides
authors.initials: A
authors.lastname: Antsaklis
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Anagnou
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D002940:Circadian Rhythm / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D016640:Diabetes, Gestational / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy; D055815:Young Adult
chemical_list: D056930:ARNTL Transcription Factors