@article{TEXTUAL,
      recid = {10765},
      author = {Rangel, Marina and Santos, Jéssica Cassilla dos and Ortiz,  Paula Helena Lima and Hirata, Mario and Jasiulionis, Miriam  Galvonas and Araujo, Ronaldo C. and Ierardi, Daniela  Filippini and Franco, Maria do Carmo},
      title = {Modification of Epigenetic Patterns in Low Birth Weight  Children: Importance of Hypomethylation of the  &amp;lt;i&amp;gt;ACE&amp;lt;/i&amp;gt; Gene Promoter},
      journal = {PLOS ONE},
      address = {2014-08-29},
      number = {TEXTUAL},
      abstract = {&lt;p&gt;There is a growing body of evidence that epigenetic  alterations are involved in the pathological mechanisms of  many chronic disorders linked to fetal programming.  Angiotensin-converting enzyme (ACE) appears as one  candidate gene that brings new insights into the epigenetic  control and later development of diseases. In this view, we  have postulated that epigenetic modifications in the  &lt;em&gt;ACE&lt;/em&gt; gene might show different interactions between  birth weight (BW), blood pressure levels, plasma ACE  activity and ACE I/D polymorphism. To explore this  hypothesis, we performed a cross-sectional study to  evaluate the DNA methylation of 3 CpG sites using  pyrosequencing within the &lt;em&gt;ACE&lt;/em&gt; gene promoter of  peripheral blood leukocytes from 45 LBW children compared  with 70 NBW children. Our results have revealed that LBW  children have lower methylation levels (&lt;em&gt;P&lt;&lt;/em&gt;0.001)  in parallel with a higher ACE activity  (&lt;em&gt;P = &lt;/em&gt;0.001). Adjusting for prematurity, gender,  age, body mass index, and family history of cardiovascular  disease did not alter these findings. We have also  performed analyses of individual CpG sites. The frequency  of DNA methylation was significantly different at two CpG  sites (site 1: nucleotide position +555; and site 3:  nucleotide position +563). In addition, we have found a  significant inverse correlation between degree of DNA  methylation and both ACE activity (&lt;em&gt;P&lt;/em&gt;&lt;0.001) and  systolic blood pressure levels (&lt;em&gt;P&lt;/em&gt;&lt;0.001). We also  observed that the methylation level was significantly lower  in LBW children who are carriers of the DD genotype  compared to NBW children with DD genotype  (&lt;em&gt;P&lt;/em&gt;&lt;0.024). In conclusion, we are able to  demonstrate that the hypomethylation in the 3 CpG sites of  &lt;em&gt;ACE&lt;/em&gt; gene promoter is associated with LBW in 6 to  12 year-old children. The magnitude of these epigenetic  changes appears to be clinically important, which is  supported by the observation that discrete changes in DNA  methylation can affect systolic blood pressure and ACE  protein activity levels.&lt;/p&gt;},
      url = {http://knowledge.uchicago.edu/record/10765},
}