DNMT1 and DNMT3B Gene Variants and Their Association with Endometriosis in South Indian Women

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2021 Oct 26

PMID 34697715

Citations 3

Authors

K V Veena

Swapna Siddamalla

Mamata Deenadayal

Sisinthy Shivaji

Manjula Bhanoori

Affiliations

Soon will be listed here.

Abstract

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.

Methods: 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 (D') for pairwise linkage disequilibrium (LD) were surveyed by Haploview Software.

Result: 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.

Conclusion: 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.

Citing Articles

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References

Zondervan K, Becker C, Koga K, Missmer S, Taylor R, Vigano P . Endometriosis. Nat Rev Dis Primers. 2018; 4(1):9. DOI: 10.1038/s41572-018-0008-5. View

Parasar P, Ozcan P, Terry K . Endometriosis: Epidemiology, Diagnosis and Clinical Management. Curr Obstet Gynecol Rep. 2017; 6(1):34-41. PMC: 5737931. DOI: 10.1007/s13669-017-0187-1. View

Sachedina A, Todd N . Dysmenorrhea, Endometriosis and Chronic Pelvic Pain in Adolescents. J Clin Res Pediatr Endocrinol. 2020; 12(Suppl 1):7-17. PMC: 7053437. DOI: 10.4274/jcrpe.galenos.2019.2019.S0217. View

Bhanoori M, Deenadayal M, Kennedy S, Shivaji S . The G2964A 3'-untranslated region polymorphism of the signal transducer and activator of transcription 6 gene is associated with endometriosis in South Indian women. Hum Reprod. 2007; 22(4):1026-30. DOI: 10.1093/humrep/del486. View

Bhanoori M, Kameshwari D, Zondervan K, Deenadayal M, Kennedy S, Shivaji S . The endothelial nitric oxide synthase Glu298Asp polymorphism is not a risk factor for endometriosis in south Indian women. Eur J Obstet Gynecol Reprod Biol. 2008; 139(1):53-8. DOI: 10.1016/j.ejogrb.2008.01.006. View

Govatati S, Tangudu N, Deenadayal M, Chakravarty B, Shivaji S, Bhanoori M . Association of E-cadherin single nucleotide polymorphisms with the increased risk of endometriosis in Indian women. Mol Hum Reprod. 2011; 18(5):280-7. DOI: 10.1093/molehr/gar079. View

Govatati S, Kodati V, Deenadayal M, Chakravarty B, Shivaji S, Bhanoori M . Mutations in the PTEN tumor gene and risk of endometriosis: a case-control study. Hum Reprod. 2013; 29(2):324-36. DOI: 10.1093/humrep/det387. View

Govatati S, Challa K, Reddy S, Pramod K, Deenadayal M, Chakravarty B . BRCA1 alterations are associated with endometriosis, but BRCA2 alterations show no detectable endometriosis risk: a study in Indian population. J Assist Reprod Genet. 2014; 32(2):277-85. PMC: 4354195. DOI: 10.1007/s10815-014-0379-9. View

Tempfer C, Simoni M, Destenaves B, Fauser B . Functional genetic polymorphisms and female reproductive disorders: part II--endometriosis. Hum Reprod Update. 2008; 15(1):97-118. PMC: 2639061. DOI: 10.1093/humupd/dmn040. View

10.

Guo S . Epigenetics of endometriosis. Mol Hum Reprod. 2009; 15(10):587-607. DOI: 10.1093/molehr/gap064. View

11.

Rajendran G, Shanmuganandam K, Bendre A, Muzumdar D, Mujumdar D, Goel A . Epigenetic regulation of DNA methyltransferases: DNMT1 and DNMT3B in gliomas. J Neurooncol. 2011; 104(2):483-94. DOI: 10.1007/s11060-010-0520-2. View

12.

Moore L, Le T, Fan G . DNA methylation and its basic function. Neuropsychopharmacology. 2012; 38(1):23-38. PMC: 3521964. DOI: 10.1038/npp.2012.112. View

13.

Zhang W, Xu J . DNA methyltransferases and their roles in tumorigenesis. Biomark Res. 2017; 5:1. PMC: 5251331. DOI: 10.1186/s40364-017-0081-z. View

14.

Houshdaran S, Nezhat C, Vo K, Zelenko Z, Irwin J, Giudice L . Aberrant Endometrial DNA Methylome and Associated Gene Expression in Women with Endometriosis. Biol Reprod. 2016; 95(5):93. PMC: 5178151. DOI: 10.1095/biolreprod.116.140434. View

15.

Wu Y, Strawn E, Basir Z, Halverson G, Guo S . Aberrant expression of deoxyribonucleic acid methyltransferases DNMT1, DNMT3A, and DNMT3B in women with endometriosis. Fertil Steril. 2006; 87(1):24-32. DOI: 10.1016/j.fertnstert.2006.05.077. View

16.

Deng N, Zhou H, Fan H, Yuan Y . Single nucleotide polymorphisms and cancer susceptibility. Oncotarget. 2018; 8(66):110635-110649. PMC: 5746410. DOI: 10.18632/oncotarget.22372. View

17.

Cheng P, Chen H, Zhang R, Liu S, Zhou-Cun A . Polymorphism in DNMT1 may modify the susceptibility to oligospermia. Reprod Biomed Online. 2014; 28(5):644-9. DOI: 10.1016/j.rbmo.2014.01.003. View

18.

Haggarty P, Hoad G, Horgan G, Campbell D . DNA methyltransferase candidate polymorphisms, imprinting methylation, and birth outcome. PLoS One. 2013; 8(7):e68896. PMC: 3724884. DOI: 10.1371/journal.pone.0068896. View

19.

Jaiswal S, Sukla K, Kumari N, Lakhotia A, Kumar A, Rai A . Maternal risk for down syndrome and polymorphisms in the promoter region of the DNMT3B gene: a case-control study. Birth Defects Res A Clin Mol Teratol. 2015; 103(4):299-305. DOI: 10.1002/bdra.23348. View

20.

Coppede F, Bosco P, Tannorella P, Romano C, Antonucci I, Stuppia L . DNMT3B promoter polymorphisms and maternal risk of birth of a child with Down syndrome. Hum Reprod. 2012; 28(2):545-50. DOI: 10.1093/humrep/des376. View