Association of HLA-DQ2 and HLA-DQ8 risk alleles to intestinal injury and serology in patients with celiac disease

Costa, Mônica Schiavon; Pegoraro, Giovana Ribeiro; Silva, Clédia Silveira Flores da; Schneider, Augusto; Schadock, Ines; Botelho, Fabiana Torma; Barros, Carlos Castilho

doi:10.1590/1678-9865202437e220188

home Sumário navigate_before Anterior Atual Seguinte navigate_next

home Sumário

ORIGINAL | Clinical Nutrition • Rev Nutr 37 • 2024 • https://doi.org/10.1590/1678-9865202437e220188 linkcopy

Association of HLA-DQ2 and HLA-DQ8 risk alleles to intestinal injury and serology in patients with celiac disease

Associação dos alelos de risco HLA-DQ2 e HLA-DQ8 à lesão intestinal e sorologia em pacientes com doença celíaca

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective This study aims to describe the distribution of main celiac disease risk alleles related to human leucocyte antigen complex and their association to the severity of intestinal injury, serological test results, CD-associated diseases and symptomatology.

Methods The DNA of 140 celiac disease patients was analyzed, and the distribution of the three most important risk alleles to the celiac disease development was identified (DQA1*05:01, DQB1*02:01 and DRB1*04, the last one as a DQB1*03:02/DQA1*03/DRB1*04 haplotype marker). Data on serological tests, biopsy results, symptomatology and incidence of CD-associated diseases were collected by using a previously validated questionnaire.

Results It was found that 98% of patients presented at least one copy of the studied alleles. Patients carrying simultaneously both HLA-DQ2 risk alleles were highly prevalent (75%), and 20.7% patients carried the HLA-DQ8 haplotype. Positive patients for both HLA-DQ2 risk alleles presented positive association to anti-gliadin (p=0.037), anti-endomysium (p=0.001) and anti-transglutaminase (p=0.032) serological tests, and a higher prevalence of osteoporosis and hypothyroidism. Patients carrying one or none of those alleles often presented negative serological results. In addition, it was found an association between intestinal injury severity and genetic profile (No-BreakpNo-Break<0.001).

Conclusion Results suggest that the HLA-DQ genotyping are associated to serological tests and the severity of intestinal damage in celiac disease patients.

Keywords
Autoimmune enteropathy; Genetic markers; Gluten

Genetic Profiles		Prevalence of genetic profile	Anemia	Mouth ulcers	Problems to gain weight	Weight loss	Skin injuries	Difficulty gaining height	Abdominal distension	Abdominal pain	Diarrhea	Constipation
Combined analysis
	Negative for all studied alleles	3 (2.1)	1 (33.31)	1 (33.3)	1 (33.3)	0 (0.0)	1 (33.3)	1 (33.3)	2 (66.7)	3 (100.0)	2 (66.7)	2 (66.7)
	DQA1*05:01	5 (3.6)	1 (20.0)	5 (100.0)	3 (60.0)	5 (100.0)	2 (40.0)	1 (20.0)	5 (100.0)	5 (100.0)	4 (80.0)	3 (60.0)
	DQB1*02:01	11 (7.9)	7 (63.4)	3 (27.3)	2 (18.2)	4 (36.4)	5 (45.5)	2 (18.2)	10 (90.9)	7 (63.3)	6 (54.6)	5 (45.5)
	DQA105:01 + DQB102:01	92 (65.7)	40 (43.5)	34 (37.0)	36 (39.1)	31 (34.1)	27 (29.4)	15 (16.3)	69 (75.0)	65 (70.7)	57 (62.0)	42 (45.6)
Combined analysis
	DRB1*04	11 (7.9)	3 (27.3)	4 (36.4)	4 (36.4)	5 (45.6)	7 (63.6)	2 (18.2)	8 (72.7)	9 (81.8)	7 (63.6)	5 (45.6)
	DQA105:01 + DRB104	1 (0.7)	1 (100.0)	0 (0.0)	1 (100.0)	1 (100.0)	1 (100.0)	0 (0.0)	0(0.0)	1 (100.0)	1 (100.0)	0 (0.0)
	DQB102:01 + DRB104	4 (2.9)	3 (75.0)	2 (50.0)	2 (50.0)	2 (50.0)	2 (50.0)	3 (75.0)	4 (100.0)	3 (75.0)	1 (25.0)	3 (75.0)
	DQA105:01 + DQB102:01 + DRB1*04	13 (9.3)	9 (69.2)	6 (46.2)	4 (30.8)	4 (37.7)	4 (30.8)	2 (15.4)	10 (76.9)	9 (69.2)	6 (46.2)	7 (53.9)
	Fisher’s exact p-value		0.168	0.167	0.657	0.057	0.247	0.226	0.455	0.833	0.715	0.915
	DQ2 isolated analysis
	Negative for DQA105:01 + DQB102:01	14 (10.0)	4 (28.6)	5 (35.7)	5 (35.7)	5 (35.7)	8 (57.1)	3 (21.4)	10 (71.4)	12 (85.7)	9 (64.3)	7 (50.0)
	DQA1*05:01	6 (4.3)	2 (33.3)	5 (83.3)	4 (66.7)	6 (100.0)^#	3 (50.0)	1 (16.7)	5 (83.3)	6 (100.0)	5 (83.3)	3 (50.0)
	DQB1*02:01	15 (10.7)	10 (66.7)	5 (33.3)	4 (26.7)	6 (40.0)	7 (46.7)	5 (33.3)	14 (93.3)	10 (66.8)	7 (46.7)	8 (53.3)
	DQA105:01 + DQB102:01	105 (75.0)	49 (46.7)	40 (38.1)	40 (38.1)	35 (33.7)	31 (29.5)	17 (16.2)	79 (75.2)	74(70.5)	63(60.0)	49 (46.7)
Fisher’s exact p-value			0.274	0.226	0.532	0.021	0.165	0.288	0.305	0.886	0.682	0.949
DQ8 isolated analysis
	Negative for DRB1*04	111 (79.3)	49 (46.4)	43 (38.7)	42 (37.8)	40 (36.4)	35 (31.5)	19 (17.2)	86 (77.5)	80 (72.1)	69 (62.2)	52 (46.9)
	DRB1*04	29 (20.7)	16 (55.2)	12 (41.4)	11 (37.9)	12 (41.4)	14 (48.3)	7 (24.1)	22 (75.9)	22 (75.9)	15 (51.7)	15 (51.7)
Fisher’s exact p-value			0.195	0.556	0.464	0.512	0.130	0.339	0.589	0.476	0.191	0.554
Total prevalence		140 (100.0)	65 (46.4)	55 (39.3)	53 (37.9)	52 (37.4)	49 (35.0)	26 (18.6)	108 (77.1)	102 (72.9)	84 (60.0)	67 (47.9)

Genetic profiles		Prevalence n (%)
Combined analysis
	Negative for all studied alleles	3 (2.1)
	DQA1*05:01	5 (3.6)
	DQB1*02:01	11 (7.9)
	DQA105:01 + DQB102:01	92 (65.7)
	DRB1*04	11 (7.9)
	DQA105:01 + DRB104	1 (0.7)
	DQB102:01 + DRB104	4 (2.9)
	DQA105:01 + DQB102:01 + DRB1*04	13 (9.3)
Total positives		137 (97.9)
DQ2 isolated analysis
	Negative for DQA105:01 + DQB102:01	14 (10.0)
	DQA1*05:01	6 (4.3)
	DQB1*02:01	15 (10.7)
	DQA105:01 + DQB102:01	105 (75.0)
Total positives		126 (90.0)
DQ8 isolated analysis
	Negative for DRB1*04	111 (79.3)
	DRB1*04	29 (20.7)

Genetic profiles		Prevalence of genetic profile	Lactose intolerance	Hypothyroi dism	Osteopenia	Dermatitis herpetiformis	Allergy to cow’s milk protein	Repetition abortions	Infertility	Autoimmune thyroid disease	Osteoporosis	Type 1 diabetes Mellitus
Genetic profiles		n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)
Combined analysis
	Negative for all studied alleles	3 (2.1)	3 (100.0)	1 (33.3)	0 (0.0)	1 (33.3)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
	DQA1*05:01	5 (3.6)	3 (60.0)	2 (40.0)	2 (40.0)	0 (0.0)	2 (40.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
	DQB1*02:01	11 (7.9)	9 (81.8)	3 (27.3)	2 (18.2)	2 (18.2)	2 (18.2)	2 (18.2)	0 (0.0)	1 (9.1)	0 (0.0)	0 (0.0)
	DQA105:01 + DQB102:01	92 (65.7)	43 (46.7)	23 (25.0)	17 (18.5)	11 (12.0)	5 (5.4)	4 (4.4)	4 (4.4)	5 (5.4)	4 (4.4)	2 (2.2)
	DRB1*04	11 (7.9)	4 (36.4)	1 (9.1)	2 (18.2)	2 (18.2)	2 (18.2)	1 (9.1)	1 (9.1)	0 (0.0)	1 (9.1)	1 (9.1)
	DQA105:01 + DRB104	1 (0.7)	1 (100.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
	DQB102:01 + DRB104	4 (2.9)	2 (50.0)	1 (25.0)	1 (25.0)	1 (25.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	1 (0.7)	0 (0.0)
	DQA105:01 + DQB102:01 + DRB1*04	13 (9.3)	4 (30.8)	2 (15.4)	2 (15.4)	0 (0.0)	1 (7.7)	1 (7.7)	2 (15.4)	0 (0.0)	0 (0.0)	0 (0.0)
Fisher’s exact p-value			0.085	0.822	0.891	0.106	0.147	0.422	0.527	0.856	0.412	0.598
DQ2 isolated analysis
	Negative for DQA105:01 + DQB102:01	14 (10.0)	7 (50.0)	2 (14.3)	2 (14.3)	3 (21.4)	2 (14.3)	1 (7.1)	1 (7.1)	0 (0.0)	1 (7.1)	1 (7.1)
	DQA1*05:01	6 (4.3)	4 (66.7)	2 (33.3)	2 (33.3)	0 (0.0))	2 (33.3)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
	DQB1*02:01	15 (10.7)	11 (73.3)	4 (26.7)	3 (20.0)	3 (20.0)	2 (13.3)	2 (13.3)	0 (0.0)	1 (6.7)	1 (6.7)	0 (0.0)
	DQA105:01 + DQB102:01	105 (75.0)	47 (44.8)	25 (23.8)	19 (18.1)	11 (10.5)	6 (5.7)	5 (4.8)	6 (5.7)	5 (4.8)	4 (3.8)	2 (1.9)
Fisher’s exact p-value			0.223	0.959	0.536	0.620	0.610	0.338	0.747	0.838	0.564	0.402
DQ8 isolated analysis
	Negative for DRB1*04	111 (79.3)	58 (52.3)	29 (26.1)	21 (19.2)	14 (12.6)	9 (8.1)	6 (5.4)	4 (3.6)	6 (5.4)	4 (3.6)	2 (1.8)
	DRB1*04	29 (27.7)	11 (37.9)	4 (13.8)	5 (17.2)	3 (10.3)	3 (10.3)	2 (6.9)	3 (10.3)	0 (0.0)	2 (6.9)	1 (3.6)
Fisher’s exact p-value			0.235	0.342	0.798	0.764	0.522	0.563	0.182	0.338	0.614	0.531
Total prevalence			69 (49.3)	33 (23.6)	26 (18.6)	17 (12.1)	12 (8.6)	8 (5.7)	7 (5.0)	6 (4.3)	6 (4.3)	3 (2.1)

Genetic Profiles		Positive serological test results
		Anti-gliadin (n=65)		Anti-endomysium (n=70)		Anti-transglutaminase (n=81)
		n (%)	Fisher’s exact p-value	n (%)	Fisher’s exact p-value	n (%)	Fisher’s exact p-value
Combined analysis
	Negative for all studied alleles	1 (100.0)	1	1 (100.0)	1	1 (100.0)	1
	DQA1*05:01	0 (0.0)	0.058	0 (0.0)	0.043	1 (33.3)	0.056
	DQB1*02:01	3 (42.9)	0.056	3 (50.0)	0.108	4 (80.0)	0.561
	DQA105:01 + DQB102:01	34 (85.0)	0.037	44 (91.7)	<0.001	53 (91.4)	0.032
	DRB1*04	4 (80.0)	1	1 (33.3)	0.114	1 (25.0)	0.009
	DQA105:01 + DRB104	0 (0.0)	–	0 (0.0)	–	0 (0.0)	–
	DQB102:01 + DRB104	2 (66.7)	1	1 (50.0)	0.385	2 (100.0)	1
	DQA105:01 + DQB102:01 + DRB1*04	5 (71.4)	1	5 (62.5)	0.355	7 (87.5)	1
Fisher’s exact p-value		0.030		<0.001		0.006
DQ2 isolated analysis
	Negative for DQA105:01 + DQB102:01	5 (83.3)	1	2 (50.0)	0.199	2 (40.0)	0.022
	DQA1*05:01	0 (0.00)	0.058	0 (0.0)	0.043	1 (33.3)	0.056
	DQB1*02:01	5 (50.0)	0.103	4 (50.0)	0.058	6 (85.7)	1
	DQA105:01 + DQB102:01	39 (83.0)	0.05	49 (87.5)	0.001	60 (90.9)	0.007
Fisher’s exact p-value		0.018		<0.001		0.001
DQ8 isolated analysis
	Negative for DRB1*04	38 (76.0)	0.514	48 (84.2)	0.026	59 (88.1)	0.240
	DRB1*04	11 (73.3)	0.514	7 (53.9)	0.026	10 (71.4)	0.240
Fisher’s exact p-value		0.514		0.013		0.240
Total		49 (75.4)		55 (78.6)		29 (85.2)

vertical_align_top show_chart

more_horiz close
- image
- translate
- link
- article
- vertical_align_top
- file_download
- show_chart
- image
- translate
- link
- article

location_on

Pontifícia Universidade Católica de Campinas Núcleo de Editoração SBI - Campus II , Av. John Boyd Dunlop, s/n. - Prédio de Odontologia, 13059-900 Campinas - SP Brasil, Tel./Fax: +55 19 3343-6875 - Campinas - SP - Brazil
E-mail: sbi.submissionrn@puc-campinas.edu.br

rss_feed Acompanhe os números deste periódico no seu leitor de RSS

[1] Note: DQA1*05:01, DQB1*02:01, DRB1*04: names of the main risk alleles for celiac disease.