Nandini Mukherjee, Elijah H. Bolin, Amna Qasim, Mohammed S. Orloff, Philip J. Lupo, Wendy N. Nembhard
{"title":"Lamin A/C 基因的 DNA 甲基化与先天性心脏病有关。","authors":"Nandini Mukherjee, Elijah H. Bolin, Amna Qasim, Mohammed S. Orloff, Philip J. Lupo, Wendy N. Nembhard","doi":"10.1002/bdr2.2381","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Prior studies report associations of maternal serum Lamin A, encoded by the <i>LMNA</i> gene, with fetal congenital heart disease (CHD). It is unknown whether DNA methylation (DNAm) of cytosine-phosphate-guanine (CpG) sites in <i>LMNA</i> impacts the CHD susceptibility.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We investigated the associations of <i>LMNA</i> DNAm with CHD using publicly available data of CHD cases (<i>n</i> = 197) and controls (<i>n</i> = 134) from the Gene Expression Omnibus repository. Peripheral blood DNAm was measured using Illumina 850 K BeadChip for cases and 450 K BeadChip for controls. We tested 31 <i>LMNA</i> CpGs to identify differences in DNAm between cases and controls using linear regression correcting for multiple testing with false discovery rate (FDR). In a case-only analysis, we tested the variations in <i>LMNA</i> DNAm between CHD subtypes. To identify the consistency of DNAm across tissue types we compared peripheral blood (<i>n</i> = 197) and heart tissue DNAm (<i>n</i> = 20) in CHD cases.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>After adjusting for age, sex, and cell types there were significant differences in 17 of the 31 <i>LMNA</i> CpGs between CHD cases and controls (FDR <i>p</i> ≤ .05). We identified lower DNAm of cg09820673 at 3′ UTR for hypoplastic left heart syndrome compared to other CHD subtypes. Three CpGs exhibited uniform DNAm in blood and heart tissues in cases. Eleven CpGs showed changes in the same direction in blood and heart tissues in cases compared to controls.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>We identify statistically significant differences in <i>LMNA</i> DNAm between CHD cases and controls. Future studies should investigate the role of maternal <i>LMNA</i> DNAm in CHD development.</p>\n </section>\n </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 7","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2381","citationCount":"0","resultStr":"{\"title\":\"DNA methylation of the Lamin A/C gene is associated with congenital heart disease\",\"authors\":\"Nandini Mukherjee, Elijah H. Bolin, Amna Qasim, Mohammed S. Orloff, Philip J. Lupo, Wendy N. Nembhard\",\"doi\":\"10.1002/bdr2.2381\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Prior studies report associations of maternal serum Lamin A, encoded by the <i>LMNA</i> gene, with fetal congenital heart disease (CHD). It is unknown whether DNA methylation (DNAm) of cytosine-phosphate-guanine (CpG) sites in <i>LMNA</i> impacts the CHD susceptibility.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We investigated the associations of <i>LMNA</i> DNAm with CHD using publicly available data of CHD cases (<i>n</i> = 197) and controls (<i>n</i> = 134) from the Gene Expression Omnibus repository. Peripheral blood DNAm was measured using Illumina 850 K BeadChip for cases and 450 K BeadChip for controls. We tested 31 <i>LMNA</i> CpGs to identify differences in DNAm between cases and controls using linear regression correcting for multiple testing with false discovery rate (FDR). In a case-only analysis, we tested the variations in <i>LMNA</i> DNAm between CHD subtypes. To identify the consistency of DNAm across tissue types we compared peripheral blood (<i>n</i> = 197) and heart tissue DNAm (<i>n</i> = 20) in CHD cases.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>After adjusting for age, sex, and cell types there were significant differences in 17 of the 31 <i>LMNA</i> CpGs between CHD cases and controls (FDR <i>p</i> ≤ .05). We identified lower DNAm of cg09820673 at 3′ UTR for hypoplastic left heart syndrome compared to other CHD subtypes. Three CpGs exhibited uniform DNAm in blood and heart tissues in cases. Eleven CpGs showed changes in the same direction in blood and heart tissues in cases compared to controls.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>We identify statistically significant differences in <i>LMNA</i> DNAm between CHD cases and controls. 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DNA methylation of the Lamin A/C gene is associated with congenital heart disease
Background
Prior studies report associations of maternal serum Lamin A, encoded by the LMNA gene, with fetal congenital heart disease (CHD). It is unknown whether DNA methylation (DNAm) of cytosine-phosphate-guanine (CpG) sites in LMNA impacts the CHD susceptibility.
Methods
We investigated the associations of LMNA DNAm with CHD using publicly available data of CHD cases (n = 197) and controls (n = 134) from the Gene Expression Omnibus repository. Peripheral blood DNAm was measured using Illumina 850 K BeadChip for cases and 450 K BeadChip for controls. We tested 31 LMNA CpGs to identify differences in DNAm between cases and controls using linear regression correcting for multiple testing with false discovery rate (FDR). In a case-only analysis, we tested the variations in LMNA DNAm between CHD subtypes. To identify the consistency of DNAm across tissue types we compared peripheral blood (n = 197) and heart tissue DNAm (n = 20) in CHD cases.
Results
After adjusting for age, sex, and cell types there were significant differences in 17 of the 31 LMNA CpGs between CHD cases and controls (FDR p ≤ .05). We identified lower DNAm of cg09820673 at 3′ UTR for hypoplastic left heart syndrome compared to other CHD subtypes. Three CpGs exhibited uniform DNAm in blood and heart tissues in cases. Eleven CpGs showed changes in the same direction in blood and heart tissues in cases compared to controls.
Conclusion
We identify statistically significant differences in LMNA DNAm between CHD cases and controls. Future studies should investigate the role of maternal LMNA DNAm in CHD development.
期刊介绍：
The journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. In particular the journal is devoted to the publication of original scientific research that contributes to the understanding of the biology of embryonic development and the prenatal causative factors and mechanisms leading to adverse pregnancy outcomes, namely structural and functional birth defects, pregnancy loss, postnatal functional defects in the human population, and to the identification of prenatal factors and biological mechanisms that reduce these risks.
Adverse reproductive and developmental outcomes may have genetic, environmental, nutritional or epigenetic causes. Accordingly, the journal Birth Defects Research takes an integrated, multidisciplinary approach in its organization and publication strategy. The journal Birth Defects Research contains separate sections for clinical and molecular teratology, developmental and reproductive toxicology, and reviews in developmental biology to acknowledge and accommodate the integrative nature of research in this field. Each section has a dedicated editor who is a leader in his/her field and who has full editorial authority in his/her area.
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