Influence of the presence of mannose-binding lectin polymorphisms on the occurrence of leishmaniasis: a systematic review and meta-analysis

Vital, Wonei de Seixas; Santos, Felipe Jules de Araújo; Gonçalves, Maurício Leandro Fernandes; Wyrepkowski, Claudia Dantas Comandolli; Ramasawmy, Rajendranath; Furtado, Silvania da Conceição

doi:10.1016/j.abd.2021.08.004

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Original Article • An. Bras. Dermatol. 97 (3) • May-Jun 2022 • https://doi.org/10.1016/j.abd.2021.08.004 copy

Influence of the presence of mannose-binding lectin polymorphisms on the occurrence of leishmaniasis: a systematic review and meta-analysis^☆ ☆ Study conducted at the Universidade Federal do Amazonas, Manaus, AM, Brazil.

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background

Leishmaniasis is caused by an intracellular protozoan of the Leishmania genus. Mannose-binding lectin (MBL) is a serum complement protein and recognizes lipoprotein antigens in protozoa and the bacterial plasma membrane. Nucleotide variants in the promoter region and exon 1 of the MBL gene can influence its expression or change its molecular structure.

Objective

To evaluate, through a systematic review, case-control studies of the genetic association of variants in the MBL2 gene and the risk of developing leishmaniasis.

Methods

This review carried out a search in PubMed, Science Direct, Cochrane Library, Scopus and Lilacs databases for case-control publications with six polymorphisms in the mannose-binding Lectin gene. The following strategy was used: P = Patients at risk of leishmaniasis; I = Presence of polymorphisms; C = Absence of polymorphisms; O = Occurrence of leishmaniasis. Four case/control studies consisting of 791 patients with leishmaniasis and 967 healthy subjects (Control) are included in this meta-analysis. The association of variants in the mannose-binding Lectin gene and leishmaniasis under the allelic genetic model, -550 (Hvs. L), -221 (X vs. Y), +4 (Q vs. P), CD52 (A vs. D), CD54 (A vs. B), CD57 (A vs. C) and A/O genotype (A vs. O) was evaluated. International Prospective Register of Systematic Reviews (PROSPERO): CRD42020201755.

Results

The meta-analysis results for any allelic genetic model showed no significant association for the variants within the promoter, the untranslated region, and exon 1, as well as for the wild-type A allele and mutant allele O with leishmaniasis.

Study limitations

Caution should be exercised when interpreting these results, as they are based on a few studies, which show divergent results when analyzed separately.

Conclusions

This meta-analysis showed a non-significant association between the rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, and rs1800451 polymorphisms of the Mannose-binding Lectin gene and leishmaniasis in any allelic and heterogeneous evaluation.

Keywords
Leishmaniasis; Mannose-binding lectin; Polymorphism, genetic

Study	Selection				Comparability			Outcome
	Representativeness	Selection of the non-exposed cohort	Investigation	Final score not present at the start	Comparability (confounding)	Evaluation of outcomes	Duration/Screening	Monitoring of adequacy	Total
Felipe FJ	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	**	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	9
Salsabil H	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	**	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	9
Alonso DP	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	8
Anshuman M	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	^* * ), with the exception of comparability, which allowed for two points.	8

Year	Study	Country/Region	Ethnic group	Clinical forms	Case Control samples		Age, mean years ± SD or mean (range) Case Control		SNPs
2007	Alonso DP	Brazil/Northeast	Mixed	VL	61	231	6 months to 73 years	6 months to 73 years	rs11003125, rs7096206, rs5030737, rs1800450, rs1800451
2015	De Araújo FJ	Brazil/ North	Mixed	CL	400	382	311 men (32 ± 15.5 years)	225 men (38 ± 17.6 years)	rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, rs1800451
2015	De Araújo FJ	Brazil/ North	Mixed	CL	400	382	89 women (32 ± 13.7)	157 women (34 ± 17.5)
2013	Salsabil H	Morocco/North	African	VL	112	139	7 ± 12 years	8.5 ± 12 years	rs7096206, rs1800450, rs1800451
2015	Anshuman M	India	NR	VL	218	215	28,7 ± 16.7 years	35.3 ± 16.2 years	rs7095891

Study	Year	Total sample		Case					Control
-550		Cases	Control	HH	HL	LL	H	L	HH	HL	LL	H	L
Alonso DP	2007	60	226	4 (7)	29 (48)	27 (45)	37 (31)	83 (69)	25 (11)	99 (44)	102 (45)	149 (33)	303 (67)
de Araújo FJ	2015	365	332	49 (13)	167 (46)	149 (41)	265 (36)	465 (64)	53 (16)	147 (44)	132 (40)	253 (38)	411 (62)
-221				XX	XY	YY	X	Y	XX	XY	YY	X	Y
Alonso DP	2007	60	226	0 (0)	14 (23)	46 (77)	14 (12)	106 (88)	4 (2)	64 (28)	158 (70)	72 (16)	380 (84)
Salsabiln H	2013	112	139	15 (13)	39 (34)	58 (52)	69 (31)	155 (69)	20 (14)	71 (51)	48 (35)	111 (40)	167 (60)
de Araújo FJ	2015	365	332	30 (08)	125 (34)	210 (58)	185 (25)	545 (75)	12 (4)	77 (23)	243 (73)	101 (15)	563 (85)
+4				QQ	QP	PP	Q	P	QQ	QP	PP	Q	P
de Araújo FJ	2015	365	332	17 (5)	95 (26)	253 (69)	129 (18)	601 (82)	9 (3)	94 (28)	229 (69)	111 (17)	551 (83)
Anshuman M	2015	218	215	12 (6)	72 (33)	134 (61)	96 (22)	340 (78)	22 (10)	83 (39)	110 (51)	127 (29)	303 (71)
CD52				AA	AD	DD	A	D	AA	AD	DD	A	D
Alonso DP	2007	61	231	58 (95)	3 (5)	0 (0)	119 (98)	3 (2)	218 (94)	12 (5.1)	1 (0.9)	448 (97)	14 (3)
de Araújo FJ	2015	366	332	342 (93)	22 (6)	2 (1)	706 (96)	26 (04)	306 (92)	26 (8)	0 (0)	638 (96)	26 (4)
CD54				AA	AB	BB	A	B	AA	AB	BB	A	B
Alonso DP	2007	61	231	41 (67)	19 (31)	1 (2)	101 (83)	21 (17)	117 (51)	96 (41)	18 (8)	330 (71)	132 (29)
Salsabiln H	2013	104	133	71 (68)	27 (26)	6 (6)	169 (81)	39 (19)	96 (72)	32 (24)	5 (4)	224 (84)	42 (16)
de Araújo FJ	2015	366	332	215 (59)	121 (33)	30 (8)	551 (75)	181 (25)	211 (63)	105 (32)	16 (5)	527 (79)	137 (21)
CD57				AA	AC	CC	A	C	AA	AC	CC	A	C
Alonso DP	2007	61	231	55 (90)	6 (10)	0 (0)	116 (95)	6 (5)	202 (87)	28 (12)	1 (1)	432 (94)	30 (6)
Salsabiln H	2013	104	133	88 (85)	15 (14)	1 (1)	176 (91)	17 (9)	111 (83)	18 (14)	4 (3)	240 (90)	26 (10)
de Araújo FJ	2015	365	332	255 (70)	91 (25)	19 (5)	601 (82)	129 (18)	270 (81)	57 (17)	5 (2)	597 (90)	67 (10)
A/O				AA	AO	OO	A	O	AA	AO	OO	A	O
Alonso DP	2007	61	231	36 (59)	20 (33)	5 (8)	92 (75)	30 (25)	95 (41)	103 (45)	33 (14)	293 (63)	169 (37)
de Araújo FJ	2015	365	332	126 (35)	155 (42)	84 (23)	407 (56)	323 (44)	153 (46)	133 (40)	46 (14)	439 (66)	225 (34)

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[1] ∗Corresponding author. E-mail:wonei.vital@pucpr.edu.br (W.S. Vital).

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Influence of the presence of mannose-binding lectin polymorphisms on the occurrence of leishmaniasis: a systematic review and meta-analysis☆ ☆ Study conducted at the Universidade Federal do Amazonas, Manaus, AM, Brazil.

Abstract

Background

Objective

Methods

Results

Study limitations

Conclusions

Influence of the presence of mannose-binding lectin polymorphisms on the occurrence of leishmaniasis: a systematic review and meta-analysis^☆ ☆ Study conducted at the Universidade Federal do Amazonas, Manaus, AM, Brazil.