Endocrine Abstracts (2012) 29 OC15.4

The DNA methylation as a predisposition factor in the pathogenesis of congenital hypothyroidism in premature infants

F. Marelli1,4, D. Gentilini1, G. Weber2, M. Vigone2, G. Radetti3 & L. Persani1,4


1IRCCS Istituto Auxologico Italiano, Cusano Milanino, Italy; 2HSR Istutito Salute e Vita San Raffaele, Milan, Italy; 3Compensorio sanitario di Bolzano, Bolzan, Italy; 4University of Milan, Milan, Italy.


Introduction: Epidemiological data indicate that children born prematurely have a risk 3–5 fold higher of congenital hypothyroidism (CH). In addition premature infants born small for gestational age (SGA) have a risk of 12% higher to develop IC compared to prematures with appropriate development (AGA). The mechanisms that justify the increased risk of IC are still unknown. Some studies report a pattern of aberrant methylation associated with prematurity, intrauterine fetal development and the onset of some diseases. This project is focused on the study of DNA methylation, as predisposing factor of thyroid diseases.

Methods: Using the Illumina Infinium-HumanMethylation27 technology we analyzed the global DNA methylation patterns (AVGβ) and selected the differentially methylated genes (DMGs) between 31 CH-cases born premature, AGA or SGA, and 31 term or preterm controls. The following groups were selected according to the gestational age at birth: 12 CH-with severe prematurity (CH-SP<32 weeks) and 19 CH-premature infants (CH-P 32–37 weeks); Controls: 9-CPS, 6-CP, 12-term birth (CT>37 weeks). The same subjects were then analyzed according to intrauterine growth (20 CH-SGA, 11 CH-AGA than 6 C-SGA and 20 C-AGA) or the degree of CH: 19 with overt CH (CH-O, TSH>10 μU/l) and 12 with mild CH (CHM, TSH<10 μU/l) than 16 CP and 12 CT.

Results and Conclusions: The global and gene-specific methylation analysis showed that infants born prematurely and SGA have a significant hypomethylation than term-controls. The 95% of the DMGs are hypomethylated and the 70% are represented by CpG sites located in DNA non-coding regions. The gene ontology analysis revealed that DMGs involved in fetal growth and thyroid hormone metabolism were deregulated. In conclusion, these data suggests that genomic instability caused by global hypomethylation maybe related to premature birth and fetal growth delay. Thyroid defects could be caused by an increased expression of predisposing-genes, rather than a reduced expression of protective-genes.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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