The major circadian pacemaker ARNT-like protein-1 (BMAL1) is associated with susceptibility to gestational diabetes mellitus
| Autor: | Nicholas P. Anagnou, Zoe Iliodromiti, Eleni Anastasiou, Kalliopi I. Pappa, Aristides Antsaklis, Maria Gazouli |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
endocrine system medicine.medical_specialty Genotype endocrine system diseases Endocrinology Diabetes and Metabolism Single-nucleotide polymorphism Type 2 diabetes Biology Polymorphism Single Nucleotide Young Adult Endocrinology Pregnancy Polymorphism (computer science) Internal medicine Internal Medicine medicine Humans Genetic Predisposition to Disease Haplotype Case-control study ARNTL Transcription Factors nutritional and metabolic diseases General Medicine medicine.disease female genital diseases and pregnancy complications Circadian Rhythm Gestational diabetes Minor allele frequency Diabetes Gestational Diabetes Mellitus Type 2 Haplotypes Case-Control Studies Female |
| Zdroj: | Diabetes Research and Clinical Practice. 99:151-157 |
| ISSN: | 0168-8227 |
| DOI: | 10.1016/j.diabres.2012.10.015 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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