Polymorphisms of the Vitamin D Receptor Gene in Crohn’s Disease

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions of the gastrointestinal tract. Studies have shown that polymorphisms of the vitamin D receptor (VDR) gene may help elucidate the pathogenesis of CD.

Objectives

To analyze the role of VDR gene polymorphisms (ApaI, BsmI, FokI, and TaqI) in the development of CD.

Methods

The present study is a systematic review with meta-analysis. a total of 50 articles in English and Portuguese published from 2000 to 2020 were selected from 3 databases. The relationship between CD and the VDR gene was addressed in 16 articles.

Results

The TaqI polymorphism was analyzed in 3,689 patients and 4,645 control subjects (odds ratio [OR]=0.948; 95% confidence interval [95%CI]=0.851-1.056; p=0.3467). The ApaI polymorphism was studied in 3,406 patients and 4,415 control subjects (OR=1,033; 95%CI=0.854-1.250; p=0.7356). For FokI polymorphism, there were 2,998 patients and 4,146 control subjects (OR=0.965; 95%CI=0.734-1.267; p=0.7958). Lastly, the BsmI polymorphism was analyzed in 2,981 patients and 4,477 control subjects (OR=1,272; 95%CI=0.748-2.161; p=0.3743).

Conclusion

These four VDR gene polymorphisms were not associated with CD. Therefore, further studies with larger samples are required to corroborate or rectify the conclusions from the present meta-analysis.

Keywords:
genetic polymorphism; vitamin D; Crohn’s disease

N	Authors and year	Cases (n)	TaqI		Controls (n)	TaqI		OR	95%CI		Weight
N	Authors and year	Cases (n)	Negative	Positive	Controls (n)	Negative	Positive	OR	Inferior	Superior	Weight
1	Chen et al.,⁸8 Chen M, Peyrin-Biroulet L, Xia B, Guéant-Rodriguez RM, Bronowicki JP, Bigard MA, Guéant JL. Methionine synthase A2756G polymorphism may predict ulcerative colitis and methylenetetrahydrofolate reductase C677T pancolitis, in Central China. BMC Med Genet 2008;9(78) 2008	167	147	20	40	36	4	0.817	0.263	2.538	2.99
2	Gisbert-Ferrándiz et al.,³3 Gisbert-Ferrándiz L, Salvador P, Ortiz-Masiá D, et al. A single nucleotide polymorphism in the Vitamin Dreceptor gene is associatedwith decreased levels of the protein and a penetrating pattern in Crohn's disease. Inflamm Bowel Dis 2018;24(07):1462-1470 2018	103	44	59	72	31	41	0.986	0.537	1.812	10.38
3	Hughes et al.,⁴4 Hughes DJ, McManus R, Neary P, O'morain C, O'sullivan M. Common variation in the vitamin D receptor gene and risk of inflammatory bowel disease in an Irish case-control study. Eur J Gastroenterol Hepatol 2011;23(09):807-812 2011	413	148	265	699	250	449	1.003	0.778	1.293	59.68
4	Luo et al.,⁵5 Luo YY, Shu XL, Zhao H, et al. Association between vitamin D receptor gene polymorphisms and pediatric Crohn's disease in China: A study based on gene sequencing. Chin J Contemporary Pediatr 2013;15(11):1006-1008 2013	122	109	13	19	18	1	0.466	0.057	3.782	0.88
5	Martin et al.,⁹9 Martin K, Radlmayr M, Borchers R, Heinzlmann M, Folwaczny C. Candidate genes colocalized to linkage regions in inflammatory bowel disease. Digestion 2002;66(02):121-126 2002	95	37	58	119	31	88	1.811	1.013	3.238	11.38
6	Naderi et al.,¹⁰10 Naderi N, Farnood A, Habibi M, et al. Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease. J Gastroenterol Hepatol 2008;23(12): 1816-1822 2008	80	39	41	150	67	83	1.178	0.684	2.030	12.99
7	Noble et al.,¹¹11 Noble CL, McCullough J HoW, et al. Lowbody mass not vitamin D receptor polymorphisms predict osteoporosis in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2008;27 (07):588-596 2008	286	173	113	250	156	94	0.923	0.651	1.308	31.57
9	Szymczak-Tomczak et al.,¹²12 Szymczak-Tomczak A, Krela-Kazmierczak I, Kaczmarek-Rys M, et al. Vitamin Dreceptor (VDR) TaqI polymorphism, vitamin Dand bone mineral density in patients with inflammatory bowel diseases. Adv Clin Exp Med 2019;28(07):955-960 2019	85	71	14	39	36	3	0.423	0.114	1.566	2.24
10	Wang et al.,¹³13 Wang L,Wang ZT, Hu JJ, Fan R, Zhou J, Zhong J. Polymorphisms of the vitamin D receptor gene and the risk of inflammatory bowel disease: a meta-analysis. Genet Mol Res 2014;13(02): 2598-2610 2014	1,796	296	1,500	2,647	502	2,145	0.843	0.720	0.988	153.77
11	Xia et al.,¹⁴14 Xia SL, Lin XX, Guo MD, et al. Association of vitamin D receptor gene polymorphisms and serum25-hydroxyvitaminDlevels with Crohn's disease in Chinese patients. J Gastroenterol Hepatol 2016; 31(04):795-801 2016	297	272	25	446	381	65	1.856	1.141	3.020	16.21
Total		3,689	1,420	2,269	4,645	1,572	3,073	0.948	0.851	1.056	p = 0.3467

N	Authors and year	Cases (n)	ApaI		Controls (n)	ApaI		OR	95%CI		Weight
N	Authors and year	Cases (n)	Negative	Positive	Controls (n)	Negative	Positive	OR	Inferior	Superior	Weight
1	Chen et al.,⁸8 Chen M, Peyrin-Biroulet L, Xia B, Guéant-Rodriguez RM, Bronowicki JP, Bigard MA, Guéant JL. Methionine synthase A2756G polymorphism may predict ulcerative colitis and methylenetetrahydrofolate reductase C677T pancolitis, in Central China. BMC Med Genet 2008;9(78) 2008	167	117	50	40	28	12	1.020	0.486	2.144	6.97
2	Hughes et al.,⁴4 Hughes DJ, McManus R, Neary P, O'morain C, O'sullivan M. Common variation in the vitamin D receptor gene and risk of inflammatory bowel disease in an Irish case-control study. Eur J Gastroenterol Hepatol 2011;23(09):807-812 2011	413	151	262	699	226	473	1.207	0.935	1.557	59.04
3	Luo et al.,⁵5 Luo YY, Shu XL, Zhao H, et al. Association between vitamin D receptor gene polymorphisms and pediatric Crohn's disease in China: A study based on gene sequencing. Chin J Contemporary Pediatr 2013;15(11):1006-1008 2013	122	68	54	19	12	7	0.754	0.285	1.995	4.06
4	Naderi et al.,¹⁰10 Naderi N, Farnood A, Habibi M, et al. Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease. J Gastroenterol Hepatol 2008;23(12): 1816-1822 2008	80	37	43	150	50	100	1.716	0.988	2.980	12.59
5	Noble et al.,¹¹11 Noble CL, McCullough J HoW, et al. Lowbody mass not vitamin D receptor polymorphisms predict osteoporosis in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2008;27 (07):588-596 2008	286	156	130	250	133	117	1.056	0.751	1.483	33.27
6	Simmons et al.,¹⁵15 Simmons JD, Mullighan C,Welsh KI, Jewell DP. Vitamin D receptor gene polymorphism: association with Crohn's disease susceptibility. Gut 2000;47(02):211-214 2000	245	128	117	164	88	76	0.945	0.637	1.404	24.59
7	Wang et al.,¹³13 Wang L,Wang ZT, Hu JJ, Fan R, Zhou J, Zhong J. Polymorphisms of the vitamin D receptor gene and the risk of inflammatory bowel disease: a meta-analysis. Genet Mol Res 2014;13(02): 2598-2610 2014	1796	700	1096	2647	1179	1468	0.795	0.704	0.898	258.51
8	Xia et al.,¹⁴14 Xia SL, Lin XX, Guo MD, et al. Association of vitamin D receptor gene polymorphisms and serum25-hydroxyvitaminDlevels with Crohn's disease in Chinese patients. J Gastroenterol Hepatol 2016; 31(04):795-801 2016	297	153	144	446	223	223	1.110	0.829	1.486	45.06
Total		3,406	1,510	1,896	4,415	1,939	2,476	1.033	0.854	1.250	p = 0.7356

N	Authors and year	Cases (n)	FokI		Controls (n)	FokI		OR	95%CI		Weight
N	Authors and year	Cases (n)	Negative	Positive	Controls (n)	Negative	Positive	OR	Inferior	Superior	Weight
1	Chen et al.,⁸8 Chen M, Peyrin-Biroulet L, Xia B, Guéant-Rodriguez RM, Bronowicki JP, Bigard MA, Guéant JL. Methionine synthase A2756G polymorphism may predict ulcerative colitis and methylenetetrahydrofolate reductase C677T pancolitis, in Central China. BMC Med Genet 2008;9(78) 2008	167	151	16	40	34	6	1.730	0.649	4.610	4.00
2	Hughes et al.,⁴4 Hughes DJ, McManus R, Neary P, O'morain C, O'sullivan M. Common variation in the vitamin D receptor gene and risk of inflammatory bowel disease in an Irish case-control study. Eur J Gastroenterol Hepatol 2011;23(09):807-812 2011	413	159	254	699	285	414	0.910	0.709	1.167	62.06
3	Naderi et al.,¹⁰10 Naderi N, Farnood A, Habibi M, et al. Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease. J Gastroenterol Hepatol 2008;23(12): 1816-1822 2008	80	22	58	150	81	69	0.328	0.183	0.587	11.34
4	Simmons et al.,¹⁵15 Simmons JD, Mullighan C,Welsh KI, Jewell DP. Vitamin D receptor gene polymorphism: association with Crohn's disease susceptibility. Gut 2000;47(02):211-214 2000	245	141	104	164	93	71	1.035	0.695	1.542	24.20
5	Wang et al.,¹³13 Wang L,Wang ZT, Hu JJ, Fan R, Zhou J, Zhong J. Polymorphisms of the vitamin D receptor gene and the risk of inflammatory bowel disease: a meta-analysis. Genet Mol Res 2014;13(02): 2598-2610 2014	1796	698	1098	2647	971	1676	1.097	0.970	1.241	252.03
6	Xia et al.,¹⁴14 Xia SL, Lin XX, Guo MD, et al. Association of vitamin D receptor gene polymorphisms and serum25-hydroxyvitaminDlevels with Crohn's disease in Chinese patients. J Gastroenterol Hepatol 2016; 31(04):795-801 2016	297	78	219	446	93	353	1.352	0.958	1.907	325.45
Total		2,998	1,249	1,749	4,146	1,557	2,589	0.965	0.734	1.267	p = 0.7958

N	Authors and year	Cases (n)	BsmI		Controls (n)	BsmI		OR	95%CI		Weight
N	Authors and year	Cases (n)	Negative	Positive	Controls (n)	Negative	Positive	OR	Inferior	Superior	Weight
1	Chen et al.,⁸8 Chen M, Peyrin-Biroulet L, Xia B, Guéant-Rodriguez RM, Bronowicki JP, Bigard MA, Guéant JL. Methionine synthase A2756G polymorphism may predict ulcerative colitis and methylenetetrahydrofolate reductase C677T pancolitis, in Central China. BMC Med Genet 2008;9(78) 2008	167	153	14	40	36	4	1.305	0.427	3.990	3.08
2	Dresner-Pollak et al.,²2 Dresner-Pollak R, Ackerman Z, Eliakim R, Karban A, Chowers Y, Fidder HH. The BsmI vitamin D receptor gene polymorphism is associated with ulcerative colitis in Jewish Ashkenazi patients. Genet Test 2004;8(04):417-420 2004	228	83	145	495	190	305	0.920	0.665	1.273	36.53
3	Hughes et al.,⁴4 Hughes DJ, McManus R, Neary P, O'morain C, O'sullivan M. Common variation in the vitamin D receptor gene and risk of inflammatory bowel disease in an Irish case-control study. Eur J Gastroenterol Hepatol 2011;23(09):807-812 2011	413	140	273	699	260	439	0.867	0.672	1.118	59.21
4	Naderi et al.,¹⁰10 Naderi N, Farnood A, Habibi M, et al. Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease. J Gastroenterol Hepatol 2008;23(12): 1816-1822 2008	80	16	64	150	38	112	0.748	0.389	1.436	9.01
5	Wang et al.,¹³13 Wang L,Wang ZT, Hu JJ, Fan R, Zhou J, Zhong J. Polymorphisms of the vitamin D receptor gene and the risk of inflammatory bowel disease: a meta-analysis. Genet Mol Res 2014;13(02): 2598-2610 2014	1796	1083	713	2647	1031	1616	2.380	2.105	2.690	255.59
6	Xia et al.,¹⁴14 Xia SL, Lin XX, Guo MD, et al. Association of vitamin D receptor gene polymorphisms and serum25-hydroxyvitaminDlevels with Crohn's disease in Chinese patients. J Gastroenterol Hepatol 2016; 31(04):795-801 2016	297	275	22	446	380	66	2.140	1.295	3.537	15.21
Total		2,981	1,750	1,231	4,477	1,935	2,542	1.272	0.748	2.161	p = 0.3743

Sociedade Brasileira de Coloproctologia Av. Marechal Câmara, 160/916, 20020-080 Rio de Janeiro/RJ Brasil, Tel.: (55 21) 2240-8927, Fax: (55 21) 2220-5803 - Rio de Janeiro - RJ - Brazil
E-mail: sbcp@sbcp.org.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] Address for correspondence Antonio Márcio Teodoro Cordeiro Silva, D.Sc., Escola de Ciências Médicas, Farmacêuticas e Biomédicas, Pontifícia Universidade Católica de Goiás, Avenida Universitária, 1.440, Setor Universitário, Campus 1, Área 4, Goiânia, Goiás, 74605-010, Brazil (e-mail: marciocmed@gmail.com).