Evaluation of HLA-DQ2 and HLA-DQ8 haplotypes in patients with endometriosis, A case-control study

Andres, Marina P.; Peloggia, Alessandra; Abrao, Henrique M.; Magalhaes, Thais F.; Siufi Neto, João; Abrão, Mauricio Simões

doi:10.1016/j.clinsp.2023.100317

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Sumário

Original articles • Clinics 79 • 2024 • https://doi.org/10.1016/j.clinsp.2023.100317 copy

Evaluation of HLA-DQ2 and HLA-DQ8 haplotypes in patients with endometriosis, A case-control study

Authorship SCIMAGO INSTITUTIONS RANKINGS

Highlights

Celiac disease and endometriosis share inflammatory markers and pathophysiology.

HLA-DQ2 and/or HLA-DQ8 were similar between the control and endometriosis groups.

Anti- transglutaminase igA was similar between the control and endometriosis groups.

HLA-DQ2 and DQ8 had no difference in age, symptoms, endometriosis stage or location.

Abstract

Objective

To evaluate the relationship between genetic haplotypes associated with celiac disease (Human Leucocyte Antigen [HLA] DQ2 and DQ8) with the diagnosis, clinical presentation, and location of endometriosis in Brazilian women.

Method

A retrospective cross-sectional study, was conducted in a Tertiary hospital.

Patients

Women aged 18-50 years who underwent HLA-DQ2 and HLA-DQ8 haplotype analysis.

Intervention

The patients were divided into endometriosis and control groups and evaluated for symptoms; endometriosis location, American Society for Reproductive Medicine (ASRM) stage, and the presence of anti-tissue transglutaminase IgA (anti-TgA), HLA-DQ2, and HLA-DQ8 markers.

Results

A total of 434 consecutive patients with (n = 315) and without (n = 119) endometriosis were included. Pain and infertility were more frequent in the endometriosis group than in the control group. The presence of HLA-DQ2, HLA-DQ8, and anti-TgA was similar between both groups. The presence of HLA-DQ2 and HLA-DQ8 markers did not differ based on age, pain symptoms, ASRM stage, or endometriosis location.

Conclusion

Although there are similarities in inflammatory markers and pathophysiology between celiac disease and endometriosis, this study found no significant associations in the presence of HLA-DQ2 or HLA-DQ8 haplotypes and endometriosis.

Keywords
Endometriosis; Celiac Disease; HLA-DQ2; HLA-DQ8; Anti-tissue transglutaminase IgA

	Control (n = 119)	Endometriosis (n = 315)
Characteristics	Mean ± SD	Mean ± SD	p
Age (years)	39.1 ± 10.8	36.9 ± 7.3	0.05^a
Dysmenorrhea (VAS)	4.5 ± 3.9	7.1 ± 3.0	<0.001^a
Chronic pelvic pain (VAS)	1.9 ± 3.1	3.6 ± 3.8	<0.001^a
Deep dyspareunia (VAS)	2.3 ± 3.4	4.2 ± 3.6	<0.001^a
Cyclic dysuria (VAS)	0.4 ± 1.7	0.6 ± 2.0	0.132^a
Cyclic dyschezia (VAS)	1.0 ± 2.6	2.7 ± 3.7	<0.001^a
	Control (n = 119)	Endometriosis (n = 315)	p
	n (%)	n (%)	p
Infertility	24 (31.6)	112 (58.0)	<0.001^b
ASRM stage
Not Reported	‒	84 (26.7)
I	‒	75 (23.8)
II	‒	61 (19.3)
III	‒	33 (10.4)
IV	‒	62 (19.6)
Endometriosis type	‒
Not reported	‒	6 (1.9)
Superficial	‒	77 (24.4)
Ovarian	‒	17 (5.4)
Deep	‒	215 (68.2)
Site of deep endometriosis:
Retrocervical	‒	201 (63.8)
Bowel	‒	137 (43.5)
Bladder	‒	12 (3.8)
Anti-tissue transglutaminase IgA, n (%)	5 (5.2)	7 (2.9)	0.329^c
HLA-DQ2, n (%)	48 (40.3)	111 (35.4)	0.337^b
HLA-DQ8, n (%)	15 (12.6)	47 (15.0)	0.531^b
HLA-DQ2 or DQ8, n (%)	60 (50.4)	148 (46.9)	0.522^b

	HLA-DQ2+ (n = 111)	HLA-DQ2- (n = 203)
Characteristic	Mean ± SD	Mean ± SD	p
Age (years)	36.0 ± 7.4	37.3 ± 7.2	0.181^b b T-Student test; cFisher's Exact test; VAS, Visual Analogue Scale; ASRM, American Society for Reproductive Medicine, 1996.
Dysmenorrhea (VAS)	7.4 ± 2.7	6.9 ± 3.2	0.230^b b T-Student test; cFisher's Exact test; VAS, Visual Analogue Scale; ASRM, American Society for Reproductive Medicine, 1996.
Acyclic pain (VAS)	3.9 ± 3.8	3.5 ± 3.8	0.469^b b T-Student test; cFisher's Exact test; VAS, Visual Analogue Scale; ASRM, American Society for Reproductive Medicine, 1996.
Deep dyspareunia (VAS)	4.1 ± 3.8	4.2 ± 3.5	0.880^b b T-Student test; cFisher's Exact test; VAS, Visual Analogue Scale; ASRM, American Society for Reproductive Medicine, 1996.
Cyclic dysuria (VAS)	0.8 ± 2.1	0.6 ± 1.9	0.766^b b T-Student test; cFisher's Exact test; VAS, Visual Analogue Scale; ASRM, American Society for Reproductive Medicine, 1996.
Cyclic dyschezia (VAS)	2.9 ± 3.9	2.6 ± 3.6	0.488^b b T-Student test; cFisher's Exact test; VAS, Visual Analogue Scale; ASRM, American Society for Reproductive Medicine, 1996.
	n (%)	n (%)
Infertility	38 (62.3)	74 (56.1)	0.415^a a Chi-Squared test;
ASRM stage
I	29 (33.0)	46 (32.4)	0.969^a a Chi-Squared test;
II	22 (25.0)	39 (27.5)
III	12 (13.6)	20 (14.1)
IV	25 (28.4)	37 (26.1)
Endometriosis type
Superficial	30 (39.0)	47 (61.0)	0.788^a a Chi-Squared test;
Ovarian	6 (35.3)	11 (64.7)
Deep	74 (34.4)	140 (65.1)
Site of deep endometriosis
Retrocervical	68 (61.8)	132 (67.3)	0.329^a a Chi-Squared test;
Bowel	46 (42.2)	90 (46.4)	0.482^a a Chi-Squared test;
Bladder	5 (4.6)	7 (3.7)	0.762^c

Characteristic	HLA-DQ8+ (n = 47)	HLA-DQ8- (n = 267)	p
Characteristic	Mean ± SD	Mean ± SD	p
Age (years)	37.4 ± 5.9	36.8 ± 7.5	0.477^b b T-Student test;
Dysmenorrhea (VAS)	6.9 ± 3.0	7.1 ± 3.1	0.453^b b T-Student test;
Acyclic pain (VAS)	3.9 ± 4.1	3.6 ± 3.8	0.673^b b T-Student test;
Deep dyspareunia (VAS)	3.8 ± 3.5	4.2 ± 3.6	0.434^b b T-Student test;
Cyclic dysuria (VAS)	0.6 ± 1.9	0.7 ± 2.0	0.595^b b T-Student test;
Cyclic dyschezia (VAS)	3.5 ± 3.9	2.5 ± 3.7	0.120^b b T-Student test;
	n (%)	n (%)
Infertility	16 (55.2)	96 (58.5)	0.735^a a Chi-squared test;
ASRM stage
I	11 (29.7)	64 (33.2)	0.970^a a Chi-squared test;
II	10 (27.0)	51 (26.4)
III	5 (13.5)	27 (14.0)
IV	11 (29.7)	51 (26.4)
Endometriosis type
Superficial	12 (15.6)	65 (84.4)	0.599^a a Chi-squared test;
Ovarian	1 (5.9)	16 (94.1)
Deep	33 (15.3)	181 (84.7)
Site of deep endometriosis
Retrocervical	32 (69.6)	168 (64.6)	0.515^a a Chi-squared test;
Bowel	23 (51.1)	113 (43.8)	0.363^a a Chi-squared test;
Bladder	2 (4.4)	10 (3.9)	0.699^c c Fisher's exact test; VAS, Visual Analogue Scale; ASRM, American Society for Reproductive Medicine, 1996.

Variable	Co-variable	OR	95% IC		p^a a Multiple regression analysis. Anti TGA, Anti-tissue Transglutaminase IgA; OR, Odds Ratio; CI, Confidence Interval.
Variable	Co-variable	OR	Inferior	Superior
Dysmenorrhea	Anti TGA	0.548	0.132	2.267	0.406
	HLA-DQ2	1.168	0.717	1.904	0.532
	HLA-DQ8	1.286	0.659	2.509	0.460
	Age	0.931	0.902	0.961	0.000
Dyspareunia	Anti TGA	0.902	0.255	3.186	0.872
	HLA-DQ2	0.740	0.456	1.203	0.224
	HLA-DQ8	0.793	0.407	1.546	0.496
	Age	0.992	0.963	1.023	0.621
Dyschezia	Anti TGA	347664436.454	0.000		0.999
	HLA-DQ2	0.995	0.542	1.830	0.988
	HLA-DQ8	0.663	0.302	1.455	0.305
	Age	0.971	0.936	1.008	0.128
Dysuria	Anti TGA	0.536	0.060	4.825	0.578
	HLA-DQ2	0.394	0.123	1.256	0.115
	HLA-DQ8	66677154.537	0.000		0.998
	Age	1.012	0.946	1.082	0.724
Acyclic pain	Anti TGA	1.727	0.355	8.404	0.498
	HLA-DQ2	1.073	0.644	1.789	0.786
	HLA-DQ8	0.634	0.321	1.252	0.190
	Age	0.994	0.964	1.025	0.694
Infertility	Anti TGA	1.988	0.463	8.534	0.355
	HLA-DQ2	1.067	0.589	1.931	0.831
	HLA-DQ8	0.720	0.328	1.582	0.414
	Age	0.963	0.926	1.002	0.062
Presence of endometriosis	Anti TGA	2.047	0.594	7.058	0.256
	HLA-DQ2	1.303	0.795	2.134	0.294
	HLA-DQ8	0.771	0.372	1.600	0.485
	Age	0.975	0.947	1.004	0.091

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[1] * Corresponding author. E-mail address:msabrao@mac.com (M.S. Abrão)