@article{3156478,
    title = "The major circadian pacemaker ARNT-like protein-1 (BMAL1) is associated
with susceptibility to gestational diabetes mellitus",
    author = "Pappa, Kalliopi I. and Gazouli, Maria and Anastasiou, Eleni and and Iliodromiti, Zoe and Antsaklis, Aristides and Anagnou, Nicholas P.",
    journal = "Diabetes Research and Clinical Practice",
    year = "2013",
    volume = "99",
    number = "2",
    pages = "151-157",
    publisher = "Elsevier Ireland Ltd",
    issn = "0168-8227",
    doi = "10.1016/j.diabres.2012.10.015",
    keywords = "Gestational diabetes mellitus; BMAL1; Clock genes; Circadian rhythm;
Type 2 diabetes",
    abstract = "Aims: 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.
Conclusion: These data suggest that the impairment of the BMAL1 clock
gene expression is closely associated with GDM susceptibility. (C) 2012
Elsevier Ireland Ltd. All rights reserved."
}