Lactotransferrin gene functional polymorphisms do not influence susceptibility to human immunodeficiency virus-1 mother-to-child transmission in different ethnic groups

Zupin, Luisa; Polesello, Vania; Coelho, Antonio Victor Campos; Boniotto, Michele; Arraes, Luiz Claudio; Segat/, Ludovica; Crovella, Sergio

doi:10.1590/0074-02760140447

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Articles • Mem. Inst. Oswaldo Cruz 110 (2) • Apr 2015 • https://doi.org/10.1590/0074-02760140447 copy

Lactotransferrin gene functional polymorphisms do not influence susceptibility to human immunodeficiency virus-1 mother-to-child transmission in different ethnic groups

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Lactotransferrin, also known as lactoferrin, is an iron binding glycoprotein that displays antiviral activity against many different infectious agents, including human immunodeficiency virus (HIV)-1. Lactotransferrin is present in the breast milk and in the female genitourinary mucosa and it has been hypothesised as a possible candidate to prevent mother-to-child HIV-1 transmission. To verify if two functional polymorphisms, Thr29Ala and Arg47Lys, in the lactotransferrin encoding gene (LTF) could affect HIV-1 infection and vertical transmission, a preliminary association study was performed in 238 HIV-1 positive and 99 HIV-1 negative children from Brazil, Italy, Africa and India. No statistically significant association for the Thr29Ala and Arg47Lys LTF polymorphisms and HIV-1 susceptibility in the studied populations was found. Additionally LTF polymorphisms frequencies were compared between the four different ethnic groups.

AIDS; HIV-1; innate immunity; lactoferrin; SNPs; vertical transmission

LTF SNP Thr29Ala (rs1126477)	HIV-	HIV+	HIV- vs. HIV+ p (CI) OR
Africa	n = 15	n = 26
A	0.76 (23)	0.77 (40)	Reference
G	0.23 (7)	0.23 (12)	1.00 (0.30-3.40) 0.99
A/A	0.60 (9)	0.61 (16)	Reference
A/G	0.33 (5)	0.31 (8)	1.00 (0.19-4.64) 0.90
G/G	0.07 (1)	0.08 (2)	1.00 (0.05-73.62) 1.12
HWE (χ²; p)	0.07; 0.79	0.46; 0.50	-
India	n = 31	n = 45
A	0.47 (29)	0.39 (35)	Reference
G	0.53 (33)	0.61 (55)	0.40 (0.68-2.80) 1.38
A/A	0.13 (4)	0.16 (7)	Reference
A/G	0.68 (21)	0.47 (21)	0.51 (0.11-2.68) 0.58
G/G	0.19 (6)	0.38 (17)	0.69 (0.25-9.53) 1.59
HWE (χ²; p)	4.03; 0.04	0.01; 0.90	-
Brazil	n = 35	n = 78
A	0.51 (36)	0.52 (81)	Reference
G	0.49 (34)	0.48 (75)	1.00; (0.54-1.79) 0.98
A/A	0.31 (11)	0.32 (25)	Reference
A/G	0.40 (14)	0.40 (31)	1.00 (0.34-2.78) 0.97
G/G	0.29 (10)	0.28 (22)	1.00 (0.31-3.09) 0.97
HWE (χ²; p)	1.39; 0.24	3.24; 0.07	-
Italy	n = 18	n = 89
A	0.25 (9)	0.31 (55)	Reference
G	0.75 (27)	0.69 (123)	0.55 (0.56-3.46) 1.34
A/A	0.06 (1)	0.12 (11)	Reference
A/G	0.39 (7)	0.37 (33)	1.00; (0.32-3.61) 1.05
G/G	0.56 (10)	0.51 (45)	0.67 (0.28-115.53) 2.42
HWE (χ²; p)	0.02; 0.87	1.54; 0.21	-

LTF SNP Arg47Lys (rs1126478)	HIV-	HIV+	HIV- vs. HIV+ p (CI) OR
Africa	n = 15	n = 26
G	0.97 (29)	0.96 (50)	Reference
A	0.03 (1)	0.04 (2)	1.00 (0.06-70.74) 1.16
G/G	0.93 (14)	0.96 (25)	Not calculable
A/G	0.07 (1)	0.00 (0)	Not calculable
A/A	0.00 (0)	0.04 (1)	Not calculable
HWE (χ²; p)	0.02; 0.89	26; 3.41E-07
India	n = 31	n = 45	-
G	0.66 (41)	0.64 (58)	Reference
A	0.34 (21)	0.36 (32)	0.86 (0.52-2.26) 1.08
G/G	0.39 (12)	0.38 (17)	Reference
A/G	0.55 (17)	0.53 (24)	1.00 (0.34-2.90) 0.99
A/A	0.06 (2)	0.09 (4)	1.00 (0.17-17.82) 1.40
HWE (χ²; p)	1.56; 0.21	1.21; 0.27	-
Brazil	n = 35	n = 78
G	0.57 (40)	0.67 (104)	Reference
A	0.43 (30)	0.33 (52)	0.18 (0.36-1.24) 0.67
G/G	0.40 (14)	0.49 (38)	Reference
A/G	0.34 (12)	0.36 (28)	0.82 (0.31-2.38) 0.86
A/A	0.26 (9)	0.15 (12)	0.26 (0.15-1.64) 0.50
HWE (χ²; p)	3.15; 0.08	2.88; 0.09	-
Italy	n = 18	n = 89
G	0.36 (13)	0.40 (71)	Reference
A	0.64 (23)	0.60 (107)	0.71 (0.53-2.70) 1.17
G/G	0.06 (1)	0.16 (14)	Reference
A/G	0.61 (11)	0.48 (43)	0.79 (0.20-2.45) 0.73
A/A	0.33 (6)	0.36 (32)	0.66 (0.27-129.16) 2.58
HWE (χ²; p)	1.89; 0.17	0.005; 0.94	-

LTF SNP Thr29Ala (rs1126477)	Total (HIV+ plus HIV-)	HapMap/ 1000 Genomes	Total vs. Hapmap/ 1000 Genomes p (CI) OR
	Africa (n = 41)	HapMap-YRI^a (n = 113)
A	0.77 (63)	0.85 (192)	Reference
G	0.23 (19)	0.15 (34)	0.12 (0.85-3.32) 1.70
A/A	0.61 (25)	0.70 (79)	Reference
A/G	0.32 (13)	0.30 (34)	0.69 (0.50-2.80) 1.21
G/G	0.07 (3)	0.00 (0)	Not calculable
	India (n = 76)	1000 Genomes-ASN^b (n = 286)
A	0.42 (64)	0.40 (229)	Reference
G	0.58 (88)	0.60 (343)	0.64 (0.63-1.34) 0.92
A/A	0.14 (11)	0.17 (49)	Reference
A/G	0.55 (42)	0.46 (131)	0.38 (0.65-3.32) 1.43
G/G	0.30 (23)	0.37 (106)	1.00 (0.41-2.38) 0.97
	Brazil (n = 113)	1000 Genomes-AMR^c (n = 199)
A	0.52 (117)	0.41 (149)	Reference
G	0.48 (109)	0.59 (213)	0.01 (0.46-0.92) 0.65
A/A	0.32 (36)	0.19 (34)	Reference
A/G	0.40 (45)	0.45 (81)	0.03 (0.28-0.99) 0.53
G/G	0.28 (32)	0.36 (66)	0.02 (0.23-0.90) 0.46
	Italy (n = 107)	HapMap-TSI^d (n = 88)
A	0.30 (64)	0.26 (46)	Reference
G	0.70 (150)	0.74 (130)	0.43 (0.52-1.32) 0.83
A/A	0.11 (12)	0.06 (5)	Reference
A/G	0.37 (40)	0.41 (36)	0.27 (0.12-1.60) 0.47
G/G	0.51 (55)	0.53 (47)	0.29 (0.13-1.63) 0.49

LTF SNP Arg47Lys (rs1126478)	Total (HIV+ plus HIV-)	HapMap/ 1000 Genomes	Total vs. Hapmap/ 1000 Genomes p (CI) OR
	Africa (n = 41)	HapMap-YRI^a (n = 113)
G	0.97 (79)	0.99 (223)	Reference
A	0.03 (3)	0.01 (3)	0.19 (0.37-21.43) 2.81
G/G	0.93 (39)	0.97 (110)	Reference
A/G	0.07 (1)	0.03 (3)	1.00 (0.02-12.11) 0.94
A/A	0.00 (1)	0.00 (0)	Not calculable
	India (n = 76)	1000 Genomes-ASN^b (n = 286)
G	0.66 (99)	0.65 (371)	Reference
A	0.34 (53)	0.35 (201)	1.00 (0.66-1.46) 0.99
G/G	0.39 (29)	0.43 (124)	Reference
A/G	0.55 (41)	0.43 (123)	0.22 (0.81-2.54) 1.42
A/A	0.06 (6)	0.14 (39)	0.51 (0.21-1.78) 0.66
	Brazil (n = 113)	1000 Genomes-AMR^c (n = 199)
G	0.57 (144)	0.47 (169)	Reference
A	0.43 (82)	0.53 (193)	0.00006 (0.35-0.71) 0.50
G/G	0.40 (52)	0.24 (44)	Reference
A/G	0.34 (40)	0.45 (81)	0.002 (0.23-0.75) 0.42
A/A	0.26 (21)	0.31 (56)	0.0004 (0.16-0.63) 0.32
	Italy (n = 107)	HapMap-TSI^d (n = 88)
G	0.36 (84)	0.33 (59)	Reference
A	0.64 (130)	0.67 (117)	0.25 (0.50-1.21) 0.78
G/G	0.06 (15)	0.10 (9)	Reference
A/G	0.61 (54)	0.47 (41)	0.65 (0.28-2.16) 0.79
A/A	0.33 (38)	0.43 (38)	0.35 (0.20-1.68) 0.60

LTF haplotypes (Thr29Ala-Arg47Lys)	HIV-	HIV+	HIV- vs. HIV+ (p)
Africa	n = 30	n = 52
AG	0.77 (23)	0.77 (40)	1.00
GG	0.20 (6)	0.19 (10)
GA	0.03 (1)	0.04 (2)
AA	0.00 (0)	0.00 (0)
LD (p; D’; r²)	0.07; 0.99; 0.11	0.01; 0.99; 0.13	-
India	n = 62	n = 90
AG	0.47 (29)	0.39 (35)	0.56
GG	0.19 (12)	0.25 (23)
GA	0.34 (21)	0.36 (32)
AA	0.00 (0)	0.00 (0)
LD (p; D’; r²)	< 0.01; 0.99; 0.45	< 0.01; 0.99; 0.35	-
Brazil	n = 70	n = 156
AG	0.46 (32)	0.51 (79)	0.19
GA	0.37 (26)	0.32 (50)
GG	0.11 (8)	0.16 (25)
AA	0.06 (4)	0.01 (2)
LD (p; D’; r²)	< 0.01; 0.72; 0.41	< 0.01; 0.91; 0.45	-
Italy	n = 36	n = 178
GA	0.64 (23)	0.60 (106)	0.85
AG	0.25 (9)	0.30 (54)
GG	0.11 (4)	0.10 (17)
AA	0.00 (0)	0.01 (1)
LD (p; D’; r²)	< 0.01; 0.99; 0.59	< 0.01; 0.97; 0.63	-

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[1] + Corresponding author:ludovica.segat@burlo.trieste.it