<i>VDR</i> polymorphisms influence immunological response in HIV-1+ individuals undergoing antiretroviral therapy

Silva, Ronaldo Celerino da; Alves, Neyla Maria Pereira; Pereira, Jorge José de Souza; Coelho, Antonio Victor Campos; Arraes, Luiz Cláudio; Brandão, Lucas André Cavalcanti; Crovella, Sergio; Silva, Jaqueline de Azevêdo

doi:10.1590/1678-4685-GMB-2017-0289

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Human and Medical Genetics • Genet. Mol. Biol. 42 (2) • Apr-Jun 2019 • https://doi.org/10.1590/1678-4685-GMB-2017-0289 copy

VDR polymorphisms influence immunological response in HIV-1+ individuals undergoing antiretroviral therapy

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Vitamin D exerts an immuno-modulatory activity on several immune system cells through the vitamin D receptor (VDR). Herein, we verified that age and a therapeutic regimen containing protease inhibitors are associated with failures in antiretroviral therapies (ARVs). In addition, we assessed whether a VDR SNP (rs11568820: C allele and CC genotype) and GC (rs2228570-rs11568820) allelic combinations are associated with immunological failure (p < 0.05). Our findings suggest a possible role of VDR SNPs on immunological failure in HIV-1+ individuals undergoing regular ARVs.

Keywords:
VDR; HIV-1; ARVs; SNPs; CD4 recovery

	Virologic Response			Immunological Response
Characteristics	Success (n=132)	Failure (n=63)	Univariate analysis	Success (n=65)	Failure (n=67)	Univariate analysis
Sex, n (%)
Female	72 (54.5)	42 (66.7)	X²=2.1052, df=1, p-value= 0.147	40 (61.5)	32 (47.8)	X²=1.7736, df=1, p-value=0.183
Male	60 (45.5)	21 (33.3)		25 (38.5)	35 (52.2)
Age
Median years (IQR)	38.0 (34.0-46.0)	35.0 (31.5-41.0)	W=3201, p-value=0.009*	37.0 (34.0-46.0)	38.0 (34.0-45.0)	W=2015, p-value=0.528
Weight
Median kilograms (IQR)	62.0 (54.2-74.0)	62.7 (55.0-73.2)	W=4043.5, p-value=0.500	63.0 (53.0-74.0)	62.0 (56.0-74.0)	W=1858, p-value=0.630
Baseline viral load
Median log10 copies/mL(IQR)	4.40 (3.02-5.10)	3.78 (2.85-4.91)	W=3417.5, p-value=0.526	4.52 (3.68-5.06)	4.31 (2.36-5.11)	W=1741, p-value=0.451
CD4+ T cells count baseline
Median cells/mm³ (IQR)	282.0 (165.0-365.0)	291.0 (179.0-410.0)	W=3883, p-value=0.769	282 (200.5-433.0)	282.5 (126.0-343.7)	W=1567, p-value=0.178
HAART regimens, n (%)
NNRTI use	80 (61.1)	28 (44.4)	X²= 4.3617, df=1, p-value=0.037*	32 (53.1)	43 (68.7)	X²= 3.9558, df=1, p-value=0.047*
PI use	50 (38.9)	35 (55.6)		29 (46.9)	17 (31.3)

SNPs	Virological		Fisher’s Exact Test	Immunological		Fisher’s Exact Test
	Success n (%)	Failure n (%)	OR (95% CI),p-value	Success n (%)	Failure n (%)	OR (95% CI),p-value
rs2248098
G	125 (54.3)	52 (46.4)	Reference	62 (55.4)	63 (53.4)	Reference
A	105 (45.7)	60 (53.6)	1.37 (0.85-2.22), 0.205	50 (44.6)	55 (46.6)	1.08 (0.62-1.88), 0.792
GG	34 (29.6)	12 (21.4)	Reference	20 (35.7)	14 (23.7)	Reference
GA	57 (49.6)	28 (50.0)	1.39 (0.59-3.41), 0.551	22 (39.3)	35 (59.3)	2.25 (0.88-5.93), 0.082
AA	24 (20.9)	16 (28.6)	1.87 (0.69-5.22), 0.249	14 (25.0)	10 (16.9)	1.02 (0.31-3.34), 1.000
rs1540339
C	167 (69.6)	77 (67.5)	Reference	85 (70.8)	82 (68.3)	Reference
T	73 (30.4)	37 (32.5)	1.10 (0.66-1.82), 0.713	35 (29.2)	38 (31.7)	1.12 (0.62-2.03), 0.779
CC	59 (49.2)	28 (49.1)	Reference	31 (51.7)	28 (46.7)	Reference
CT	49 (40.8)	21 (36.8)	0.90 (0.43-1.88), 0.863	23 (38.3)	26 (43.3)	1.25 (0.55-2.86), 0.699
TT	12 (10.0)	8 (14.0)	1.40 (0.44-4.23), 0.601	6 (10.0)	6 (10.0)	1.10 (0.26-4.67), 1.000
rs2228570
G	180 (69.8)	87 (71.3)	Reference	83 (65.9)	97 (73.5)	Reference
A	78 (30.2)	35 (28.7)	0.93 (0.56-1.52), 0.811	43 (34.1)	35 (26.5)	0.70 (0.39-1.23), 0.222
GG	63 (48.8)	29 (47.5)	Reference	27 (42.9)	36 (37.9)	Reference
GA	54 (41.9)	29 (47.5)	1.16 (0.59-2.30), 0.748	29 (46.0)	25 (37.9)	0.65 (0.29-1.43), 0.269
AA	12 (9.3)	3 (4.9)	0.54 (0.09-2.24), 0.545	7 (11.1)	5 (7.6)	0.54 (0.12-2.22), 0.359
rs4760648
T	98 (53.3)	40 (58.8)	Reference	52 (55.3)	46 (51.1)	Reference
C	86 (46.7)	28 (41.2)	0.80 (0.43-1.45), 0.477	42 (44.7)	44 (48.9)	1.18 (0.66-2.20), 0.658
TT	26 (28.3)	13 (38.2)	Reference	14 (29.8)	12 (26.7)	Reference
TC	46 (50.0)	14 (41.2)	0.61 (0.23-1.65), 0.356	24 (51.1)	22 (48.9)	1.07 (0.37-3.14), 1.000
CC	20 (21.7)	7 (20.6)	0.70 (0.20-2.33), 0.593	9 (19.1)	11 (24.4)	1.41 (0.38-5.39), 0.767
rs3890733 §
C	149 (64.8)	67 (67.0)	Reference	78 (67.2)	71 (62.3)	Reference
T	81 (35.2)	33 (33.0)	0.91 (0.53-1.53), 0.801	38 (32.8)	43 (37.7)	1.24 (0.70-2.22), 0.490
CC	58 (50.4)	26 (52.0)	Reference	32 (55.2)	26 (45.6)	Reference
CT	33 (28.7)	15 (30.0)	1.01 (0.43-2.32), 1.000	14 (24.1)	19 (33.3)	1.66 (0.65-4.34), 0.280
TT	24 (20.9)	9 (18.0)	0.84 (0.30-2.19), 0.824	12 (20.7)	12 (21.1)	1.23 (0.42-3.56), 0.808
rs11568820
T	109 (45.4)	50 (46.3)	Reference	63 (51.6)	44 (37.9)	Reference
C	131 (54.6)	58 (53.7)	0.96 (0.60-1.56), 0.908	59 (48.4)	72 (62.1)	1.74 (1.01-3.03), 0.037*
TT	21 (17.5)	12 (22.2)	Reference	14 (23.0)	6 (10.3)	Reference
CT	67 (55.8)	26 (48.1)	0.68 (0.27-1.75), 0.384	35 (57.4)	32 (55.2)	2.11 (0.66-7.56), 0.203
CC	32 (26.7)	16 (29.6)	0.88 (0.31-2.47), 0.815	12 (19.7)	20 (34.5)	3.78 (1.03-15.57), 0.045*

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E-mail: editor@gmb.org.br

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[1] Send correspondence to Dr. Ronaldo Celerino da Silva. Laboratory of Immunopathology Keizo Asami (LIKA), Department of Genetics, Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego,1235, 50.670-901 Recife, PE, Brazil. E-mail: ronaldocelerino@yahoo.com.br