Genetic variants in miR-146a and miR-196a2 in endometriosis: a Brazilian study

Oliveira, Gabriela Caramano de; Cintra, Mariangela Torreglosa Ruiz; Lima, Marco Fábio Prata; Gomes, Mariana Kefalas Oliveira; Marqui, Alessandra Bernadete Trovó de

doi:10.1590/1806-9282.20231382

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Revista da Associação Médica Brasileira

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ORIGINAL ARTICLE • Rev. Assoc. Med. Bras. 70 (5) • 2024 • https://doi.org/10.1590/1806-9282.20231382 copy

Genetic variants in miR-146a and miR-196a2 in endometriosis: a Brazilian study

Authorship SCIMAGO INSTITUTIONS RANKINGS

SUMMARY

OBJECTIVE:

The aim of this study was to determine the allelic and genotypic frequencies of the polymorphisms, rs2910164 miR-146a and rs11614913 miR-196a2, by investigating their association with endometriosis.

METHODS:

This is a case–control study performed with approximately 120 women. The polymorphisms were determined by real-time polymerase chain reaction. For the statistical analysis, the chi-square and logistic regression tests were used.

RESULTS:

There were no significant differences in the genotype and allele frequencies of rs2910164 and rs11614913 between cases and controls. The frequencies in both polymorphisms are in accordance with Hardy-Weinberg equilibrium regarding miR-146a (patients: χ²=1.64, p=0.20; controls: χ²=0.25, p=0.62) and miR-196a2 (patients: χ²=0.58, p=0.44; controls: χ²=2.78, p=0.10). No relationship was observed between rs2910164 and rs11614913 and endometriosis in the inheritance models analyzed.

CONCLUSION:

In this study, our results show that the studied polymorphisms are not implicated in the development of endometriosis.

KEYWORDS
Endometriosis; MicroRNAs; Real-time polymerase chain reaction; Biomarkers; Polymorphism, genetic; Diagnosis

rs2910164 polymorphism	Patients (n=47)	Controls (n=75)	p
Genotypes	n (%)	n (%)	0.68
GG	26 (55.3)	41 (54.7)
GC	20 (42.5)	30 (40)
CC	1 (2.2)	4 (5.3)
Alleles			0.87
G	0.77	0.75
C	0.23	0.25
rs11614913 polymorphism	(n=46)	(n=69)	p
Genotypes	n (%)	n (%)	0.26
CC	14 (30.5)	26 (37.7)
CT	25 (54.3)	27 (39.1)
TT	7 (15.2)	16 (23.2)
Alleles			1.00
C	0.58	0.57
T	0.42	0.43

rs2910164 polymorphism	Patients (n=43)	Controls (n=62)	OR (95%CI)	p
Codominant	n (%)	n (%)		0.94
GG	24 (55.8)	33 (53.2)	1.00
GC	18 (41.9)	27 (43.5)	1.09 (0.49–2.42)
CC	1 (2.3)	2 (3.3)	1.45 (0.12–16.98)
Dominant				0.79
GG	24 (55.8)	33 (53.2)	1.00
GC-CC	19 (44.2)	29 (46.8)	1.11 (0.51–2.43)
Recessive				0.78
GG-GC	42 (97.7)	60 (96.8)	1.00
CC	1 (2.3)	2 (3.2)	1.40 (0.12–15.94)
rs11614913 polymorphism	(n=43)	(n=62)	OR (95%CI)	p
Codominant	n (%)	n (%)		0.32
CC	13 (30.2)	24 (38.7)	1.00
CT	23 (53.5)	24 (38.7)	0.57 (0.23–1.08)
TT	7 (16.3)	14 (22.6)	1.08 (0.35–3.36)
Dominant				0.37
CC	13 (30.2)	24 (38.7)	1.00
CT-TT	30 (69.8)	38 (61.3)	0.69 (0.30–1.57)
Recessive				0.42
CC-CT	36 (83.7)	48 (77.4)	1.00
TT	7 (16.3)	14 (22.6)	1.50 (0.55–4.10)

Study	Country	Subjects	Gynecological condition analyzed	Polymorphism(s)	Association with the gynecological condition analyzed
Chang et al.¹⁹2. Mousa M, Jefout M, Alsafar H, Becker CM, Zondervan KT, Rahmioglu N. Impact of endometriosis in women of Arab ancestry on: health-related quality of life, work productivity, and diagnostic delay. Front Glob Womens Health. 2021;2:708410. https://doi.org/10.3389/fgwh.2021.708410 https://doi.org/10.3389/fgwh.2021.708410...	Taiwan	218 cases–202 controls	Endometriosis	miR-196a2 rs11614913	miR-196a2=yes
Farsimadan et al.¹⁰10. Farsimadan M, Ismail Haje M, Khudhur Mawlood C, Arabipour I, Emamvirdizadeh A, Takamoli S, et al. MicroRNA variants in endometriosis and its severity. Br J Biomed Sci. 2021;78(4):206-10. https://doi.org/10.1080/09674845.2021.1889157 https://doi.org/10.1080/09674845.2021.18...	Iran	260 cases–260 controls	Endometriosis	miR-146a rs2910164	miR-146a=yes
	Iran			miR-196a2 rs11614913	miR-196a2=no
Hosseini et al.¹¹11. Hosseini AH, Kohan L, Aledavood A, Rostami S. Association of miR-146a rs2910164 and miR-222 rs2858060 polymorphisms with the risk of polycystic ovary syndrome in Iranian women: a case-control study. Taiwan J Obstet Gynecol. 2017;56(5):652-6. https://doi.org/10.1016/j.tjog.2017.08.014 https://doi.org/10.1016/j.tjog.2017.08.0...	Iran	205 cases–205 controls	Polycystic ovary syndrome	miR-146a rs2910164	miR-146a=yes
Ebrahimi et al.¹²12. Ebrahimi SO, Reiisi S, Parchami Barjui S. Increased risk of polycystic ovary syndrome (PCOS) associated with CC genotype of miR-146a gene variation. Gynecol Endocrinol. 2018;34(9):793-7. https://doi.org/10.1080/09513590.2018.1460341 https://doi.org/10.1080/09513590.2018.14...	Iran	180 cases–192 controls	Polycystic ovary syndrome	miR-146a rs2910164	miR-146a=yes
Li et al.¹³13. Li R, Yu Y, Jaafar SO, Baghchi B, Farsimadan M, Arabipour I, et al. Genetic variants miR-126, miR-146a, miR-196a2, and miR-499 in polycystic ovary syndrome. Br J Biomed Sci. 2022;79:10209. https://doi.org/10.3389/bjbs.2021.10209 https://doi.org/10.3389/bjbs.2021.10209...	Iran	385 cases–385 controls	Polycystic ovary syndrome	miR-146a rs2910164	miR-146a=yes
	Iran			miR-196a2 rs11614913	miR-196a2=yes
Soyman et al.¹⁴14. Soyman Z, Durmus S, Ates S, Simsek G, Sozer V, Kundaktepe BP, et al. Circulating MIR-132, MIR-146A, MIR-222, AND MIR-320 expression in differential diagnosis of women with polycystic ovary syndrome. Acta Endocrinol (Buchar). 2022;18:13-9. https://doi.org/10.4183/aeb.2022.13 https://doi.org/10.4183/aeb.2022.13...	Turkey	50 cases–50 controls	Polycystic ovary syndrome	miR-146a rs2910164	miR-146a=yes
Salimi et al.¹⁵15. Salimi S, Eskandari F, Rezaei M, Narooei-Nejad M, Teimoori B, Yazdi A, et al. The effect of miR-146a rs2910164 and miR-149 rs2292832 polymorphisms on preeclampsia susceptibility. Mol Biol Rep. 2019;46(4):4529-36. https://doi.org/10.1007/s11033-019-04908-2 https://doi.org/10.1007/s11033-019-04908...	Iran		Preeclampsia	miR-146a rs2910164	miR-146a:
		Blood: 219 cases–242 controls			Blood=yes
		Placental: 111 cases–119 controls			Placental=yes
Asadi-Tarani et al.¹⁶16. Asadi-Tarani M, Saravani M, Teimoori B, Ghasemi M, Salimi S. The relationships between maternal and placental polymorphisms of miR-196a2 and miRNA-499 genes and preeclampsia. Br J Biomed Sci. 2020;77(4):191-5. https://doi.org/10.1080/09674845.2020.1769331 https://doi.org/10.1080/09674845.2020.17...	Iran		Preeclampsia	miR-196a2 rs11614913	miR-196a2:
		Blood: 315 cases–317 controls			Blood=no
		Placental: 103 cases–133 controls			Placental=yes
Lukács et al.¹⁷17. Lukács J, Soltész B, Penyige A, Nagy B, Póka R. Identification of miR-146a and miR-196a-2 single nucleotide polymorphisms at patients with high-grade serous ovarian cancer. J Biotechnol. 2019;297:54-7. https://doi.org/10.1016/j.jbiotec.2019.03.016 https://doi.org/10.1016/j.jbiotec.2019.0...	Hungary	75 cases–75 controls	Ovarian cancer	miR-146a rs2910164	miR-146a=no
	Hungary			miR-196a2 rs11614913	miR-196a2=no
Alipour et al.¹⁸18. Alipour M, Abtin M, Hosseinzadeh A, Maleki M. Association between miR-146a C > G, miR-149 T > C, miR-196a2 T > C, and miR-499 A > G polymorphisms and susceptibility to idiopathic recurrent pregnancy loss. J Assist Reprod Genet. 2019;36(11):2237-44. https://doi.org/10.1007/s10815-019-01573-z https://doi.org/10.1007/s10815-019-01573...	Iran	120 cases–90 controls	Idiopathic recurrent	miR-146a rs2910164	miR-146a=yes
	Iran		pregnancy loss	miR-196a2 rs11614913	miR-196a2=yes
Present study	Brazil	47/46 cases	Endometriosis	miR-146a rs2910164	miR-146a=no
Present study	Brazil	75/69 controls		miR-196a2 rs11614913	miR-196a2=no

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[1] *Corresponding author: alessandra.marqui@uftm.edu.br