Autoimmunity-related <i>LINC01934</i> and <i>AP002954.4</i> lncRNA polymorphisms may be effective in pediatric celiac disease: a case-control study

Orenay-Boyacioglu, Seda; Dogan, Guzide; Caliskan, Metin; Uzuner, Esen Gul

doi:10.1590/1806-9282.20231490

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Revista da Associação Médica Brasileira

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Sumário

Original Article • Rev. Assoc. Med. Bras. 70 (4) • 2024 • https://doi.org/10.1590/1806-9282.20231490 copy

Autoimmunity-related LINC01934 and AP002954.4 lncRNA polymorphisms may be effective in pediatric celiac disease: a case-control study

Authorship SCIMAGO INSTITUTIONS RANKINGS

SUMMARY

OBJECTIVE:

Various studies have reported that certain long non-coding RNA levels are unusually low in the intestines of celiac disease patients, suggesting that this may be associated with the inflammation observed in celiac disease. Despite these studies, the research aimed at uncovering the potential role of long non-coding RNAs in the pathogenesis of autoimmune diseases like celiac disease remains insufficient. Therefore, in this study, we plan to assess long non-coding RNA polymorphisms associated with autoimmunity in children diagnosed with celiac disease according to the European Society for Paediatric Gastroenterology Hepatology and Nutrition criteria.

METHODS:

DNA was isolated from paraffin tissue samples of 88 pediatric celiac disease patients and 74 healthy pediatric individuals. Single-nucleotide polymorphism genotyping of five long non-coding RNA polymorphisms associated with autoimmunity (LINC01934-rs1018326, IL18RAP-rs917997, AP002954.4-rs10892258, UQCRC2P1-rs6441961, and HCG14 rs3135316) was conducted using the TaqMan single-nucleotide polymorphism genotyping assays with the LightCycler 480.

RESULTS:

In our study, the genotypic and allelic frequency distribution of LINC01934-rs1018326 and AP002954.4-rs10892258 polymorphisms was found to be statistically significant in the comparison between the two groups (p<0.05). According to the multiple genetic model analyses, the LINC01934-rs1018326 polymorphism was observed to confer a 1.14-fold risk in the recessive model and a 1.2-fold risk in the additive model for pediatric celiac disease. Similarly, the AP002954.4-rs10892258 polymorphism was found to pose a 1.40-fold risk in the dominant model and a 1.7-fold risk in the additive model.

CONCLUSION:

Our study results draw attention to the LINC01934-rs1018326 and AP002954.4-rs10892258 polymorphisms in celiac disease and suggest that these polymorphisms may be associated with inflammation in autoimmune diseases like celiac disease.

KEYWORDS:
Celiac disease; lncRNA; Polymorphism; Autoimmunity; Epigenetics

Demographic and clinical features			pCeD Group (n=88)	Control group (n=84)	OR (95% CI)	p-value
Gender
	Female		59.3%	61%	1.4 (0.72–2.73)	0.09
	Male		39.7%	39%
	Age (M±SD)		11.55±6.62	11.76±4.92	0.37 (0.17–0.79)	0.56
Marsh classes
	Marsh 1-2		19%	–	–	–
	Marsh 3a		22%	–	–	–
	Marsh 3b		28%	–	–	–
	Marsh 3c		31%	–	–	–
Symptoms
	Abdominal pain		79%	–	–	–
	Inability to gain weight		58%	–	–	–
	Anemia			–	–	–
		Short height	54%	–	–	–
		Constipation	20.6%	–	–	–
		Diarrhea	15.1%	–	–	–
		Vomiting	12.9%	–	–	–
		Abdominal pain	8%	–	–	–

SNP and genotypes		pCeD group (n=88)	Control group (n=84)	X²2 Rubio-Tapia A, Hill ID, Semrad C, Kelly CP, Greer KB, Limketkai BN, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023;118(1):59-76. https://doi.org/10.14309/ajg.0000000000002075 https://doi.org/10.14309/ajg.00000000000...	df	p-value
LINC01934-rs1018326
	AA	27 (30.68%)	20 (23.81%)	9.82	2	0.007^* * Significant p<0.05. HWE: Hardy-Weinberg equilibrium.
	AG	45 (51.14%)	32 (38.10%)
	GG	16 (18.18%)	32 (38.10%)
	HWE p-value	0.714	0.041^* * Significant p<0.05. HWE: Hardy-Weinberg equilibrium.
IL18RAP-rs917997
	TT	11 (12.50%)	10 (11.90%)	2.42	2	0.39
	CT	40 (45.45%)	47 (55.95%)
	CC	37 (42.05%)	27 (32.14%)
	HWE p-value	0.970	0.126
AP002954.4-rs10892258
	GG	63 (71.59%)	43 (51.19%)	8.88	2	0.01^* * Significant p<0.05. HWE: Hardy-Weinberg equilibrium.
	GA	20 (22.73%)	34 (40.48%)
	AA	5 (5.68%)	7 (8.33%)
	HWE p-value	0.065	0.611
UQCRC2P1-rs6441961
	TT	11 (12.50%)	14 (16.67%)	1.53	2	0.47
	CT	42 (47.73%)	43 (51.19%)
	CC	35 (39.77%)	27 (32.14%)
	HWE p-value	0.769	0.653
HCG14-rs3135316
	GG	78 (88.64%)	69 (82.14%)	1.98	2	0.37
	AG	7 (7.95%)	9 (10.71%)
	AA	3 (3.41%)	6 (7.14%)
	HWE p-value	0.000^* * Significant p<0.05. HWE: Hardy-Weinberg equilibrium.	0.000^* * Significant p<0.05. HWE: Hardy-Weinberg equilibrium.
Allele frequencies		pCeD group (n=88)	Control group (n=84)	X²2 Rubio-Tapia A, Hill ID, Semrad C, Kelly CP, Greer KB, Limketkai BN, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023;118(1):59-76. https://doi.org/10.14309/ajg.0000000000002075 https://doi.org/10.14309/ajg.00000000000...	df	p-value
LINC01934-rs1018326
	T	56.25%	42.85%	3.59	1	0.05^* * Significant p<0.05. HWE: Hardy-Weinberg equilibrium.
	C	43.75%	57.15%	3.59	1
lIL18RAP-rs917997
	T	35.23%	39.88%	0.46	1	0.50
	C	64.77%	60.12%	0.46	1	0.50
AP002954.4-rs10892258
	G	82.95%	71.43%	3.77	1	0.05^* * Significant p<0.05. HWE: Hardy-Weinberg equilibrium.
	A	17.05%	28.57%	3.77	1
UQCRC2P1-rs6441961
	T	36.36%	42.26%	0.73	1	0.39
	C	63.64%	57.74%	0.73	1	0.39
HCG14-rs3135316
	G	92.62%	87.50%	1.46	1	0.23
	A	7.38%	12.50%	1.46	1	0.23

lncRNA SNPs	Inheritance model	Genotype	OR (95%CI)	p-value
LINC01934-rs1018326	Recessive	AA+AG	Ref.	0.004^* * Significant p<0.05. OR (95%CI): odds ratio (95% confidence interval).
	Recessive	GG	1.14 (0.60–2.17)
	Dominant	AA	Ref.	0.312
	Dominant	GG +AG	0.65 (0.85–3.46)	0.312
	Additive	AA	Ref.	0.018^* * Significant p<0.05. OR (95%CI): odds ratio (95% confidence interval).
		AG	1.04 (0.50–2.17)
		GG	1.2 (0.54–2.62)
AP002954.4-rs10892258	Recessive	GG+GA	Ref.	0.495
	Recessive	AA	0.49 (0.15–1.64)	0.495
	Dominant	GG	Ref.	0.005^* * Significant p<0.05. OR (95%CI): odds ratio (95% confidence interval).
	Dominant	AA+GA	1.40 (0.72–2.73)
	Additive	GG	Ref.	0.015^* * Significant p<0.05. OR (95%CI): odds ratio (95% confidence interval).
		GA	1.03 (0.55–1.92)
		AA	1.7 (1.08–2.77)

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[1] *Corresponding author: sorenay@adu.edu.tr