Histone deacetylase 1, Sirtuin 1, and Sirtuin 3 single-nucleotide polymorphisms and the risk of endometriosis in South Indian women

Abstract

The aim of the study was to investigate the association between Histone deacetylase 1 (HDAC1), Sirtuin1 (SIRT1), and Sirtuin3 (SIRT3) 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 HDAC1, SIRT1, and SIRT3 SNPs (rs1741981T/C, rs144124002A/G, and rs536715G/A) was carried out on DNA from subjects by PCR-RFLP and sequencing analysis. The genotype (p = .00782) and allele (p = .02561) frequencies of the HDAC1 rs1741981 polymorphism showed significant difference between cases and controls. In contrast, SIRT1 (rs144124002) and SIRT3 (rs536715) SNPs did not show significant association with the disease. The HDAC1 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 HDAC1, SIRT1, and SIRT3 with endometriosis risk.

Impact Statement

• What is already known on this subject? 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 HDACs, is a key epigenetic mechanism of gene expression regulation in endometriosis, therefore genetic variation in HDACs causing epigenetic control defects might lead to disease susceptibility.

• What do the results of this study add? Our study shows that the HDAC1 SNP is significantly associated with endometriosis in South Indian women, whereas the SNPs of SIRT1 and SIRT3 could not show any association with the disease.

• What are the implications of these findings for clinical practice and/or further research? The polymorphism of HDAC1 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.

Keywords:

• Endometriosis
• epigenetic genes
• polymorphisms
• South Indian women

Acknowledgements

The authors are most grateful to all of the patients who participated in the present study and also sincerely thank Dr. Suresh Govatati for sample collection and DNA isolation.

Ethical approval

The Institutional review board of the Centre of Cellular and Molecular biology (CCMB), Hyderabad, approved the study (IEC/CCMB26/2008/February 6, 2008). All the participants in the study were of South Indian origin (Dravidian linguistic group).

Author contributions

KVV contributed to execution of experiments, analysis and interpretation of data, statistical analysis, and drafting of manuscript. SS contributed to data analysis. MD contributed to acquisition of data. SS contributed to analysis and interpretation of data. MB contributed to conception and design of study, analysis and interpretation of data, statistical analysis, and drafting of manuscript. All authors have seen and agreed to the ‘Author’s contribution’ statement.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported in part by grants from the SERB (DST), India (Lr. No.: SR/FT/LS-188/2009) and OU-DST PURSE Programme-II (DST Sanction No. SR/PURSE Phase 2/32(G)), Department of Science and Technology (DST), India to Dr. Manjula Bhanoori.