DNMT1 and DNMT3B gene variants and their association with endometriosis in South Indian women

Background Endometriosis is a multifactorial estrogen dependent gynecological disease characterized by implantation of functional endometrial tissue at ectopic positions. Though this disease is benign, it is associated with an increased risk of malignant transformation. Epigenetic disruptions like aberrant DNA methylation, resulting changes in gene expression capacity, are important in tumor progression and malignant cellular transformation. Therefore, variation in genes involved in DNA methylation might lead to disease susceptibility. Purpose To investigate the association between DNA methyl transferases (DNMT1 and DNMT3B) single nucleotide polymorphisms (SNPs) and the risk of endometriosis in South Indian women.

In the present study, we examined the genotypic and allele distribution of DNMT1 (rs10423341C/A, rs2228611G/Aandrs4804490C/A) and DNMT3B (rs1569686G/T) among the endometriosis patients (n = 150) and controls (n = 150). The genotypes were analyzed by polymerase chain reaction (PCR) and sequencing methods. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (Dʹ) for pairwise linkage disequilibrium (LD) were surveyed by Haploview Software.

Significant increase in the frequencies of DNMT1 rs10423341 (P = 0.04601), rs2228611 (P = 0.00175) and DNMT3B rs1569686 (P = 0.033) genotypes and alleles was observed in patients compared to controls. In addition, the frequency of A/A/C (P = 0.0065) haplotype was significantly high in patients. But the DNMT1 (rs4804490) SNP did not show significant association with the disease.

The DNMT1 and DNMT3B polymorphism may constitute an inheritable risk factor for endometriosis in South Indian women. To the best of our knowledge there is no reported study on the association of polymorphisms in DNMT1 and DNMT3B with endometriosis risk. Similar content being viewed by others Abbreviations - CI: - Confidence interval - χ2 : - Chi square - D′: - Disequilibrium coefficient - LD: - Linkage disequilibrium - HWE: - Hardy–Weinberg equilibrium - OR: - Odds ratio - DNMT1: - DNA methyl transferase 2 - DNMT3B: - DNA methyl transferase 3B - PR: - Progesterone receptor - APC: - Adenomatous polyposis coli - PTEN: - Phosphatase and tensin homologue - PCR: - Polymerase chain reaction - SNPs: - Single nucleotide polymorphisms - TSGs: - Tumor suppressor genes, - SF-1: - Steroidogenic factor-1 - ESR2: - Estrogen receptor 2

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We 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. 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. Author information Authors and Affiliations Contributions KVV: execution of experiments, analysis and interpretation of data, statistical analysis and drafting of manuscript. SS: data analysis. MD: acquisition of data. SS: analysis and interpretation of data, drafting of manuscript. MB: conception and design of study, analysis and interpretation of data, statistical analysis, drafting of manuscript. All authors will have seen and agreed to the ‘Author Contribution’ statement. Corresponding author Ethics declarations Conflict of interest The authors declare that there is no conflict of interest. Ethical approval The study was approved by the ethical committee and review board of Centre of Cellular and Molecular biology (CCMB), Hyderabad. In the study all the participants were of South Indian origin (Dravidian linguistic group). Informed consent Informed written consent form was obtained from all subjects prior to participation in this study. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions About this article Cite this article Veena, K.V., Siddamalla, S., Deenadayal, M. et al. DNMT1 and DNMT3B gene variants and their association with endometriosis in South Indian women. Mol Biol Rep 49, 321–329 (2022). https://doi.org/10.1007/s11033-021-06877-x Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s11033-021-06877-x