DOI: 10.6084/m9.figshare.20511102
title: Histone deacetylase 1, Sirtuin 1, and Sirtuin 3 single-nucleotide polymorphisms and the risk of endometriosis in South Indian women

description: The aim of the study was to investigate the association between Histone deacetylase 1 (<i>HDAC1</i>), Sirtuin1 (<i>SIRT1</i>), and Sirtuin3 (<i>SIRT3</i>) single-nucleotide polymorphisms (SNPs) and risk of endometriosis in South Indian women. A total of 300 subjects were recruited in this case-control study comprising 150 affected women and 150 women with no evidence of disease. All the subjects were of South Indian origin. The genotyping of <i>HDAC1</i>, <i>SIRT1,</i> and <i>SIRT3</i> SNPs (rs1741981T/C, rs144124002A/G, and rs536715G/A) was carried out on DNA from subjects by PCR-RFLP and sequencing analysis. The genotype (<i>p =</i> .00782) and allele (<i>p =</i> .02561) frequencies of the <i>HDAC1</i> rs1741981 polymorphism showed significant difference between cases and controls. In contrast, <i>SIRT1</i> (rs144124002) and <i>SIRT3</i> (rs536715) SNPs did not show significant association with the disease. The <i>HDAC1</i> polymorphism may constitute a heritable risk factor for endometriosis in South Indian women. To date, there is no reported study on the association of polymorphisms in <i>HDAC1</i>, <i>SIRT1</i>, and <i>SIRT3</i> with endometriosis risk.
Impact Statement<b>What is already known on this subject?</b> Endometriosis is a benign gynaecological disease characterised by the implantation of functional endometrial tissue at ectopic positions, associated with an increased risk of malignant transformation. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns. Histone modification, including deacetylation of lysine residues by <i>HDACs</i>, is a key epigenetic mechanism of gene expression regulation in endometriosis, therefore genetic variation in <i>HDACs</i> causing epigenetic control defects might lead to disease susceptibility.<b>What do the results of this study add?</b> Our study shows that the <i>HDAC1</i> SNP is significantly associated with endometriosis in South Indian women, whereas the SNPs of <i>SIRT1</i> and <i>SIRT3</i> could not show any association with the disease.<b>What are the implications of these findings for clinical practice and/or further research?</b> The polymorphism of <i>HDAC1</i> rs1741981 could be used as an important marker of genetic susceptibility to endometriosis development. Analysis of this SNP might help to identify patients at high risk for disease outcome. <b>What is already known on this subject?</b> Endometriosis is a benign gynaecological disease characterised by the implantation of functional endometrial tissue at ectopic positions, associated with an increased risk of malignant transformation. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns. Histone modification, including deacetylation of lysine residues by <i>HDACs</i>, is a key epigenetic mechanism of gene expression regulation in endometriosis, therefore genetic variation in <i>HDACs</i> causing epigenetic control defects might lead to disease susceptibility. <b>What do the results of this study add?</b> Our study shows that the <i>HDAC1</i> SNP is significantly associated with endometriosis in South Indian women, whereas the SNPs of <i>SIRT1</i> and <i>SIRT3</i> could not show any association with the disease. <b>What are the implications of these findings for clinical practice and/or further research?</b> The polymorphism of <i>HDAC1</i> rs1741981 could be used as an important marker of genetic susceptibility to endometriosis development. Analysis of this SNP might help to identify patients at high risk for disease outcome.