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Association between single nucleotide polymorphisms and viral load in congenital cytomegalovirus infection Cover

Association between single nucleotide polymorphisms and viral load in congenital cytomegalovirus infection

Open Access
|Jul 2021

Figures & Tables

Table 1

Maternal and neonatal demographic data and general characteristics of cCMV-infected infants, with subgroups of symptomatic and asymptomatic infants.

CharacteristicscCMV-infected infants (n = 92)Symptomatic infants (n = 73)Asymptomatic infants (n = 19)p-valuea
Maternal age at delivery, (years)28 (25–31)29 (25–31)28 (25–31)NS
Primipara, n (%)42 (45.65)33 (45.21)9 (47.37)NS
Preterm delivery (<37Hbd), n (%)23 (25.00)19 (26.03)4 (21.05)NS
Caesarean section, n (%)49 (54.44)45 (61.64)4 (21.05)0.006
Prenatal HCMV screening, n (%)37 (40.22)27 (36.99)10 (52.63)NS
Birth weight, (g)(21702755 –3200)(21502685 –3140)(26803050 –3630)0.028
Gestational age, (weeks)38 (37–39)38 (37–39)39 (37–40)NS
Male, n (%)46 (50.00)36 (49.32)10 (52.63)NS
Age at admission to NICU, Median (IQR), (days)16 (9–23)14 (9–21)22 (20–35)<0.001
Weight at admission to NICU, (g)3040 (2440–3450)2980 (2340–3320)3600 (2930–4310)<0.001
Age at first HCMV DNA detection in urine, (days)9 (4–15)8 (3–14)17 (8–20)0.002

Data are presented as median (IQR) or number (%).

cCMV, congenital cytomegalovirus; HCMV, human cytomegalovirus; IQR, interquartile range; NICU, Neonatal Intensive Care Unit.

a p-value for comparison between symptomatic and asymptomatic infants.

Figure 1

HCMV VL in urine depending on genotypes of IL12B rs3212227 polymorphism. Bars in the box show the first and the third quartiles. Whisker charts represent the minimum to maximum values. Small box represents median value. p-value below 0.05 is statistically significant. Kruskal-Wallis ANOVA test was used. HCMV: human cytomegalovirus; VL: viral load.

Table 2

Association between genotypes of examined polymorphisms (SNPs) and viremia and viruria in newborn infants with cCMV infection.

SNP, rs numbera, allelesGenotypen = 92, n (%)HCMV DNA (copies/mL) in bloodp-valuebHCMV DNA (copies/mL) in urinep-valuec
IL1BA/A7 (7.6)6.3 × 103 (3.8 × 103–2.7 × 104)6.5 × 106 (2.8 × 106–1.0 × 107)
rs16944A/G49 (53.3)8.6 × 103 (1.9 × 103–5.8 × 104) (n = 48)NS7.8 × 106 (5.1 × 105–1.0 × 107) (n = 48)NS
G/AG/G36 (39.1)1.5 × 104 (2.0 × 103–2.0 × 105) (n = 34)1.0 × 107 (1.7 × 106–1.0 × 107) (n = 35)
IL12BT/T57 (62.0)2.2 × 104 (2.1 × 103–1.5 × 105) (n = 54)5.8 × 106 (6.0 × 105–1.0 × 107) (n = 56)
rs3212227T/G28 (30.4)7.4 × 103 (1.8 × 103–4.7 × 104)NS1.0 × 107 (6.4 × 106–1.0 × 107) (n = 27)0.029
G/TG/G7 (7.6)4.3 × 103 (2.1 × 103–3.0 × 104)1.7 × 106 (4.2 × 105–1.0 × 107)
IL28BT/T13 (14.1)5.8 × 103 (1.9 × 103–1.3 × 105) (n = 12)2.8 × 106 (4.0 × 105–1.0 × 107) (n = 12)
rs12979860T/C38 (41.3)1.0 × 104 (1.6 × 103–1.3 × 105)NS1.0 × 107 (2.8 × 106–1.0 × 107) (n = 37)NS
C/TC/C41 (44.6)1.2 × 104 (2.1 × 103–8.2 × 104) (n = 39)8.6 × 106 (8.4 × 105–1.0 × 107)
CCL2G/G3 (3.3)2.4 × 103 (0–9.4 × 103)1.0 × 107 (9.2 × 106–1.0 × 107)
rs1024611G/A39 (42.4)1.7 × 104 (1.7 × 103–5.8 × 104) (n = 38)NS5.5 × 106 (5.2 × 105–1.0 × 107) (n = 37)NS
A/GA/A50 (54.3)8.9 × 103 (2.4 × 103–1.4 × 105) (n = 48)8.5 × 106 (1.6 × 106–1.0 × 107)
DC-SIGNG/G35 (38.0)1.2 × 104 (1.4 × 103–1.2 × 105) (n = 32)1.0 × 107 (1.3 × 106–1.0 × 107)
rs735240G/A37 (40.2)1.1 × 104 (2.4 × 103–1.7 × 105)NS7.6 × 106 (1.1 × 106–1.0 × 107) (n = 36)NS
A/GA/A20 (21.7)7.4 × 103 (1.7 × 103–3.5 × 104)5.5 × 106 (5.0 × 105–1.0 × 107) (n = 19)
TLR2G/G82 (89.1)1.2 × 104 (2.1 × 103–1.1 × 105) (n = 79)7.8 × 106 (1.2 × 106–1.0 × 107) (n = 80)
rs5743708G/A10 (10.9)4.3 × 103 (1.6 × 103–3.8 × 104)NS1.0 × 107 (1.0 × 106–1.0 × 107)NS
A/GA/A0 (0)NANA
TLR4T/T0 (0)NANA
rs4986791T/C9 (9.8)2.0 × 104 (2.8 × 103–9.8 × 104)NS1.0 × 107 (1.7 × 106–1.0 × 107)NS
C/TC/C83 (90.2)1.0 × 104 (2.0 × 103–1.0 × 105) (n = 80)8.6 × 106 (1.1 × 106–1.0 × 107) (n = 81)
TLR9T/T30 (32.6)2.4 × 104 (3.6 × 103–2.6 × 105) (n = 29)1.0 × 107 (1.7 × 106–1.0 × 107) (n = 29)
rs352140T/C47 (51.1)8.4 × 103 (2.1 × 103–5.7 × 104) (n = 45)NS5.7 × 106 (8.4 × 105–1.0 × 107) (n = 46)NS
C/TC/C15 (16.3)7.9 × 103 (1.1 × 103–3.7 × 104)1.0 × 107 (1.6 × 106–1.0 × 107)

Data are presented as median (IQR) or number (%). NS, not significant (p < 0.05).

cCMV, congenital cytomegalovirus; CCL2,C-C motif chemokine ligand 2; DC-SIGN, dendritic cell-specific ICAM-grabbing non-integrin; HCMV, human cytomegalovirus; IL, interleukin; IQR, interquartile range; NA, not applicable; SNP, single nucleotide polymorphism; TLR, toll-like receptor.

a SNP database (dbSNP) reference number (ID number).

b p-value – for comparison between genotypes and viremia.

c p-value – for comparison between genotypes and viruria.

Table 3

Association between alleles of examined polymorphisms (SNPs) and viremia and viruria in symptomatic newborn infants with cCMV infection.

SNP, rs numbera, allelesAlleleAlleles, n (%)HCMV (copies/DNA mL) in bloodp-valuebHCMV DNA (copies/mL) in urinep-valuec
IL1BG97 (66.44)2.2 × 104 (3.0 × 103–1.9 × 105) (n = 96)1.0 × 107 (2.9 × 106–1.0 × 107) (n = 94)
rs16944NSNS
G/AA49 (33.56)1.1 × 104 (3.8 × 103–5.4 × 104) (n = 48)1.0 × 107 (1.5 × 106–1.0 × 107) (n = 48)
IL12BT110 (75.34)2.6 × 104 (4.7 × 103–1.8 × 105)1.0 × 107 (1.4 × 106–1.0 × 107)
rs3212227(n = 108)0.037(n = 107)NS
G/TG36 (24.66)9.4 × 103 (2.4 × 103–3.4 × 104)1.0 × 107 (1.7 × 106–1.0 × 107) (n = 35)
IL28BC92 (63.01)1.7 × 104 (3.8 × 103–1.2 × 105)1.0 × 107 (1.7 × 106–1.0 × 107) (n = 91)
rs12979860NSNS
C/TT54 (36.99)1.9 × 104 (3.3 × 103–1.8 × 105) (n = 52)1.0 × 107 (1.6 × 106–1.0 × 107) (n = 51)
CCL2A110 (75.34)1.9 × 104 (3.9 × 103–1.7 × 105)1.0 × 107 (1.7 × 106–1.0 × 107)
rs1024611(n = 108)NS(n = 108)NS
A/GG36 (24.66)1.6 × 104 (2.0 × 103–5.4 × 104)1.0 × 107 (1.4 × 106–1.0 × 107) (n = 34)
DC-SIGNG87 (59.59)2.8 × 104 (3.9 × 103–1.5 × 105) (n = 85)1.0 × 107 (2.9 × 106–1.0 × 107) (n = 86)
rs735240NSNS
A/GA59 (40.41)1.2 × 104 (3.3 × 103–8.2 × 104)1.0 × 107 (1.5 × 106–1.0 × 107) (n = 56)
TLR2G138 (94.52)1.7 × 104 (3.7 × 103–1.5 × 105)1.0 × 107 (1.7 × 106–1.0 × 107)
rs5743708(n = 136)NS(n = 134)NS
A/GA8 (5.48)5.0 × 103 (2.8 × 103–8.4 × 104)1.0 × 107 (5.5 × 106–1.0 × 107)
TLR4 rs4986791C139 (95.21)1.7 × 104 (3.8 × 103–1.5 × 105) (n = 137)NS1.0 × 107 (1.7 × 106–1.0 × 107) (n = 135)NS
C/TT7 (4.79)3.8 × 104 (2.8 × 103–1.1 × 105)1.0 × 107 (1.7 × 106–1.0 × 107)
TLR9T84 (57.53)2.8 × 104 (3.8 × 103–1.9 × 105) (n = 83)1.0 × 107 (2.9 × 106–1.0 × 107) (n = 81)
rs352140NSNS
C/TC62 (42.47)9.4 × 103 (2.8 × 103–5.8 × 104) (n = 61)1.0 × 107 (1.6 × 106–1.0 × 107) (n = 61)

Data are presented as median (IQR) or number (%).

cCMV, congenital cytomegalovirus; CCL2, C-C motif chemokine ligand 2; DC-SIGN, dendritic cell-specific ICAM-grabbing non-integrin; HCMV, human cytomega lovirus; IL, interleukin; IQR, interquartile range; NS, not significant (p < 0.05); SNP, single nucleotide polymorphism; TLR, toll-like receptor.

a SNP database (dbSNP) reference number (ID number).

b p-value – for comparison between alleles and viremia.

c p-value – for comparison between alleles and viruria.

Table S1

Distribution of genotypes of examined SNPs in the study population of cCMV-infected infants and subgroups of symptomatic and asymptomatic newborn infants

SNP, rs numbera, allelesGenotypecCMV-infected neonates(n = 92)Symptomatic neonates (n = 73)Asymptomatic neonates (n = 19)p-valueb
Genotype frequencies, n (%)
IL1BA/A7 (7.61)5 (6.85)2 (10.53)
rs16944A/G49 (53.26)39 (53.42)10 (52.63)NS
G/AG/G36 (39.13)29 (39.73)7 (36.84)
IL12BT/T57 (61.96)43 (58.90)14 (73.68)
rs3212227T/G28 (30.43)24 (32.88)4 (21.05)NS
G/TG/G7 (7.61)6 (8.22)1 (5.26)
IL28BT/T13 (14.13)11 (15.07)2 (10.53)
rs12979860T/C38 (41.30)32 (43.84)6 (31.58)NS
C/TC/C41 (44.57)30 (41.09)11 (57.89)
CCL2G/G3 (3.26)3 (4.11)0 (0.00)
rs1024611G/A39 (42.39)30 (41.10)9 (47.37)NS
A/GA/A50 (54.35)40 (54.79)10 (52.63)
DC-SIGNG/G35 (38.04)28 (38.36)7 (36.84)
rs735240G/A37 (40.22)31 (42.47)6 (31.58)NS
A/GA/A20 (21.74)14 (19.17)6 (31.58)
TLR2G/G82 (89.13)65 (89.04)17 (89.47)
rs5743708G/A10 (10.87)8 (10.96)2 (10.53)NS
A/GA/A0 (0.00)0 (0.00)0 (0.00)
TLR4T/T0 (0.00)0 (0.00)0 (0.00)
rs4986791T/C9 (9.78)7 (9.59)2 (10.53)NS
C/TC/C83 (90.22)66 (90.41)17 (89.47)
TLR9T/T30 (32.61)23 (31.51)7 (36.84)
rs352140T/C47 (51.09)38 (52.05)9 (47.37)NS
C/TC/C15 (16.30)12 (16.44)3 (15.79)

Data are presented as number (%).

cCMV, congenital cytomegalovirus; CCL2,C-C motifchemokine ligand 2; DC-SIGN, dendritic cell-specific ICAM-grabbing non-integrin; IL, interleukin; NS, not significant (p < 0.05); SNP, single nucleotide polymorphism; TLR, toll-like receptor.

a SNP database (dbSNP) reference number (ID number).

b p-value for comparison between frequencies of genotypes and subgroups of symptomatic and asymptomatic newborn infants.

Table S2

Allele frequencies of examined SNPs in the study population in comparison to known European and Global reference populations from the Reference SNP (rs) Report

Allele frequencies, n (%)Allele frequencies, %
IL1BG320 (68.67)199 (70.57)121 (65.76)65.0149.06
rs16944NS
G/AA146 (31.33)83 (29.43)63 (34.24)34.9950.94
IL12BT352(75.54)210 (74.47)142 (77.17)77.7364.10
rs3212227NS
G/TG114 (24.46)72 (25.53)42 (22.83)22.2735.90
IL28BC309 (66.31)189 (67.02)120 (65.22)69.0964.42
rs12979860NS
C/TT157 (33.69)93 (32.98)64 (34.78)30.9135.58
CCL2A344 (73.82)205 (72.70)139 (75.54)68.3963.64
rs1024611NS
A/GG122 (26.18)77(27.30)45 (24.46)31.6136.36
DC-SIGNG278 (59.66)171 (60.64)107 (58.15)56.7664.70
rs735240NS
A/GA188 (40.34)111 (39.36)77 (41.85)43.2435.30
TLR2G441 (94.64)267 (94.68)174 (94.57)97.6199.32
rs5743708NS
A/GA25 (5.36)15 (5.32)10 (5.43)2.390.68
TLR4C440 (94.42)265 (93.97)175 (95.11)94.2395.93
rs4986791NS
C/TT26 (5.58)17 (6.03)9 (4.89)5.774.07
TLR9T269 (57.73)162 (57.45)107 (58.15)54.5741.55
rs352140NS
C/TC197 (42.27)120 (42.55)77 (41.85)45.4358.45

Data are presented as number (%).

cCMV, congenital cytomegalovirus; CCL2, C-C motifchemokine ligand 2; DC-SIGN, dendritic cell-specific ICAM-grabbing non-integrin; IL, interleukin; NS, not significant (p < 0.05); SNP, single nucleotide polymorphism; TLR, toll-like receptor.

a SNP database (dbSNP) reference number (ID number).

b p-value for comparison between frequencies of alleles and subgroups of uninfected controls and CMV-infected newborn infants.

c Reference allele frequency based on 1000Genomes study from the Reference SNP (rs) Report.

Table S3

Allele frequencies of examined SNPs in the study population of cCMV-infected neonates and subgroups of symptomatic and asymptomatic neonates

SNP,rs numbera, allelesAllelecCMV-infected infants (n = 92)Symptomatic infants (n = 73)Asymptomatic infants (n = 19)p-valueb
Allele frequencies, n (%)
IL1BG121 (65.76)97 (66.44)24 (63.16)
rs16944NS
G/AA63 (34.24)49 (33.56)14 (36.84)
IL12BT142 (77.17)110 (75.34)32 (84.21)
rs3212227NS
G/TG42 (22.83)36 (24.66)6 (15.79)
IL28BC120 (65.22)92 (63.01)28 (73.68)
rs12979860NS
C/TT64 (34.78)54 (36.99)10 (26.32)
CCL2A139 (75.54)110 (75.34)29 (76.32)
rs1024611NS
A/GG45 (24.46)36 (24.66)9 (23.68)
DC-SIGNG107 (58.15)87 (59.59)20 (52.63)
rs735240NS
A/GA77 (41.85)59 (40.41)18 (47.37)
TLR2G174 (94.57)138 (94.52)36 (94.74)
rs5743708NS
A/GA10 (5.43)8 (5.48)2 (5.26)
TLR4C175 (95.11)139 (95.21)36 (94.74)
rs4986791NS
C/TT9 (4.89)7 (4.79)2 (5.26)
TLR9T107 (58.15)84 (57.53)23 (60.53)
rs352140NS
C/TC77 (41.85)62 (42.47)15 (39.47)

Data are presented as number (%).

cCMV, congenital cytomegalovirus; CCL2, C-Cmotifchemokine ligand 2; DC-SIGN, dendritic cell-specific ICAM-grabbing non-integrin; IL, interleukin; NS, not significant (p < 0.05); SNP, single nucleotide polymorphism;; TLR, toll-like receptor.

a SNP database (dbSNP) reference number (ID number).

b p-value for comparison between frequencies of alleles and subgroups of symptomatic and asymptomatic CMV-infected newborn infants.

Table S4

Association between genotypes of examined polymorphisms and viremia and viruria in symptomatic infants with cCMV infection

SNP rs numbera allelesGenotypen = 73 n (%)HCMV DNA (copies/mL) in bloodp-valuebHCMV DNA (copies/mL) in urinep-valuec
A/A5 (6.85)6.3 × 103 (5.4 × 103–1.1 × 104)6.5 × 106 (5.4 × 106–1.0 × 107)
IL1B
rs16944A/G39 (53.42)1.9 × 104 (3.6 × 103–1.1 × 105) (n = 38)NS1.0 × 107 (1.1 × 106–1.0 × 107) (n = 38)NS
G/A
G/G29 (39.73)3.0 × 104 (2.8 × 103–2.1 × 105)1.0 × 107 (3.7 × 106–1.0 × 107) (n = 28)
T/T43 (58.90)3.9 × 104 (5.4 × 103–1.9 × 105) (n = 42)1.0 × 107 (1.3 × 106–1.0 × 107) (n = 42)
IL12B
rs3212227T/G24 (32.88)9.4 × 103 (2.4 × 103–4.7 × 104)NS1.0 × 107 (9.2 × 106–1.0 × 107) (n = 23)NS
G/T
G/G6 (8.22)7.9 × 103 (2.4 × 103–3.0 × 104)2.3 × 106 (1.6 × 106–1.0 × 107)
T/T11 (15.07)2.2 × 104 (3.3 × 103–2.1 × 105) (n = 10)7.0 × 106 (1.3 × 106–1.0 × 107) (n = 10)
IL28B
rs12979860T/C32 (43.84)1.9 × 104 (3.2 × 103–1.4 × 105)NS1.0 × 107 (3.5 × 106–1.0 × 107) (n = 31)NS
C/T
C/C30 (41.09)1.6 × 104 (3.9 × 103–1.1 × 105)1.0 × 107 (1.4 × 106–1.0 × 107)
G/G3 (4.11)2.4 × 103 (0–9.4 × 103)1.0 × 107 (9.2 × 106–1.0 × 107)
CCL2
rs1024611G/A30 (41.10)2.9 × 104 (3.6 × 103–1.1 × 105)NS1.0 × 107 (1.0 × 106–1.0 × 107) (n = 28)NS
A/G
A/A40 (54.79)1.2 × 104 (3.9 × 103–2.0 × 105) (n = 39)1.0 × 107 (3.7 × 106–1.0 × 107)
G/G28 (38.36)2.9 × 104 (4.3 × 103–1.5 × 105) (n = 27)1.0 × 107 (4.2 × 106–1.0 × 107)
DC-SIGN
rs735240G/A31 (42.47)1.2 × 104 (3.6 × 103–1.9 × 105)NS1.0 × 107 (1.4 × 106–1.0 × 107) (n = 30)NS
A/G
A/A14(19.17)1.3 × 104 (2.8 × 103–3.8 × 104)1.0 × 107 (1.7 × 106–1.0 × 107) (n = 13)
G/G65 (89.04)1.9 × 104 (3.7 × 103–1.7 × 105) (n = 64)1.0 × 107 (1.7 × 106–1.0 × 107) (n = 63)
TLR2
rs5743708G/A8 (10.96)5.0 × 103 (2.8 × 103–8.4 × 104)NS1.0 × 107 (5.5 × 106–1.0 × 107)NS
A/G
A/A0 (0.00)NANA
T/T0 (0.00)NANA
TLR4
rs4986791T/C7 (9.59)3.8 × 104 (2.8 × 103–1.1 × 105)NS1.0 × 107 (1.7 × 106–1.0 × 107)NS
C/T
C/C66 (9×0.41)1.4 × 104 (3.8 × 103–1.5 × 105) (n = 65)1.0 × 107 (1.7 × 106–1.0 × 107) (n = 64)
TLR9T/T23 (31.51)2.9 × 104 (5.3 × 103–2.6 × 105)1.0 × 107 (5.5 × 106–1.0 × 107) (n = 22)
rs352140T/C38 (52.05)1.4 × 104 (2.8 × 103–8.2 × 104) (n = 37)NS1.0 × 107 (1.1 × 106–1.0 × 107) (n = 37)NS
C/TC/C12 (16.44)8.6 × 103 (3.0 × 103–4.7 × 104)1.0 × 107 (4.3 × 106–1.0 × 107)

Data are presented as median (IQR- interquartile range) or number (%).

cCMV, congenital cytomegalovirus; CCL2, C-C motif chemokine ligand 2; DC-SIGN, dendritic cell-specific ICAM-grabbing non-integrin; HCMV, human cytomegalovirus; IL, Interleukin; NS, not significant (p < 0.05); NA, not applicable; SNP, single nucleotide polymorphism; TLR, Toll-like receptor.

a SNP database (dbSNP) reference number (ID number).

b p-value – for comparison between genotypes and viremia.

c p-value – for comparison between genotypes and viruria.

Table S5

Association between genotypes of examined polymorphisms and viremia and viruriain asymptomaticneonates with cCMV infection

SNP, rs numbera, allelesGenotypen = 19 n (%)HCMV DNA (copies/mL) in bloodp-valuebHCMV DNA (copies/mL) in urinep-valuec
IL1BA/A2 (10.53)1.4 × 104 (9.9 × 102–2.7 × 104)5.8 ×106 (2.8 × 106–8.8 × 106)
rs16944A/G10 (52.63)1.8 × 103 (3.1 × 102–4.0 × 103)NS2.7 ×105 (4.0 × 104–3.2 × 106)NS
G/AG/G7 (36.84)2.0 × 103 (1.2 × 103–2.1 × 103) (n = 5)6.9 ×105 (1.4 × 105–6.2 × 106)
IL12BT/T14 (73.68)1.8 × 103 (1.0 × 103–1.4 × 104) (n = 12)4.9 × 105 (1.4 × 105–4.6 × 106)
rs3212227T/G4 (21.05)2.0 × 103 (0–3.8 × 105)NS1.1 × 107 (1.0 × 106–4.0 × 107)NS
G/TG/G1 (5.26)2.1 × 103 (2.1 × 103–2.1 × 103)1.7 × 105 (1.7 × 105–1.7 × 105)
IL28BT/T2 (10.53)1.9 × 103 (1.2 × 103–2.7 × 103)2.7 × 105 (2.5 × 105–2.9 × 105)
rs12979860T/C6 (31.58)1.1 × 103 (0–1.6 × 103)NS2.4× 106 (1.7 × 105–6.2 × 106)NS
C/TC/C11 (57.89)2.1 × 103 (2.0 × 103–2.7 × 104) (n = 9)6.9× 105 (4.0 × 104–6.1 × 106)
CCL2G/G0 (0.00)NANA
rs1024611G/A9 (47.37)2.4 × 103 (9.5 × 102–1.5 × 104) (n = 8)NS2.5× 105 (1.4 × 105–3.2 × 106)NS
A/GA/A10 (52.63)1.2 × 103 (9.9 × 102–2.1 × 103) (n = 9)1.7× 106 (1.7 × 105–6.1 × 106)
DC-SIGNG/G7 (36.84)3.1 × 102 (0–1.2 × 103) (n = 5)2.9× 105 (3.3 × 103–2.0 × 107)
rs735240G/A6 (31.58)2.0 × 103 (1.6 × 103–2.7 × 104)NS2.6× 106 (1.7 × 105–6.2 × 106)NS
A/GA/A6 (31.58)2.4 × 103 (9.9 × 102–3.2 × 104)1.1× 106 (4.0 × 104–2.8 × 106)
TLR2G/G17 (89.47)2.1 × 103 (3.1 × 102–2.7 × 104)(n = 15)2.0× 106 (1.4 × 105–6.1 × 106)
rs5743708G/A2 (10.53)1.4 × 103 (1.2 × 103–1.6 × 103)NS2.3× 105 (1.7 × 105–2.9 × 105)NS
A/GA/A0 (0.00)NANA
TLR4T/T0 (0.00)NANA
rs4986791T/C2 (10.53)2.0 × 103 (0–4.0 × 103)NS1.0 × 107 (0–2.0 × 107)NS
C/TC/C17 (89.47)2.0 × 103 (9.9 × 102–2.7 × 104)(n = 15)6.9× 105 (1.7 × 105–4.6 × 106)
TLR9T/T7 (36.84)1.4 × 103 (0–4.0 × 103) (n = 6)2.9× 105 (1.4 × 105–2.0 × 107)
rs352140T/C9 (47.37)2.1 × 103 (1.6 × 103–1.7 × 104)(n = 8)NS6.9× 105 (1.7 × 105–4.6 × 106)NS
C/TC/C3 (15.79)3.1× 102 (0–2.7 × 104)3.2× 106 (0–8.8 × 106)

Data are presented as median (IQR- interquartile range) or number (%).

cCMV, congenital cytomegalovirus; CCL2, C-C motif chemokine ligand 2; DC-SIGN, dendritic cell-specific ICAM-grabbing non-integrin; HCMV, human cytomegalovirus; IL, Interleukin; NS, not significant (p < 0.05); NA, not applicable; SNP, single nucleotide polymorphism; TLR, Toll-like receptor.

a SNP database (dbSNP) reference number (ID number).

b p-value – for comparison between genotypes and viremia.

c p-value – for comparison between genotypes and viruria.

Table S6

Association between alleles of examined polymorphisms (SNPs) and viremia and viruria in newborn infants with cCMV infection

SNP, rs numbera, allelesAllelen, (%)HCMV DNA (copies/mL) in bloodp-valuebHCMV DNA (copies/mL) in urinep-valuec
IL1BG121 (65.76)1.2 × 104 (2.0 × 103–1.7 × 105) (n = 116)1.0 ×107 (1.1 × 106–1.0 × 107) (n = 118)
rs16944NSNS
G/AA63 (34.24)7.6 × 103 (2.4 × 103–3.8 × 104) (n = 62)6.8 ×106 (1.1 × 106–1.0 × 107) (n = 62)
IL12BT142 (77.17)1.6 × 104 (2.0 × 103–1.3 × 105) (n = 136)7.0 ×106 (1.0 × 106–1.0 × 107) (n = 139)
rs3212227NS
G/TG42 (22.83)4.8 × 103 (2.1 × 103–3.0 × 104)1.0 ×107 (1.7 × 106–1.0 × 107) (n = 41)NS
IL28BC120 (65.22)1.1 × 104 (2.1 × 103–9.0 × 104) (n = 116)8.8 ×106 (1.0 × 106–1.0 × 107) (n = 119)
rs12979860NSNS
C/TT64 (34.78)8.1 × 103 (1.6 × 103–1.3 × 105) (n = 62)7.0 ×106 (1.3 × 106–1.0 × 107) (n = 61)
CCL2A139 (75.54)1.1 × 104 (2.1 × 103–1.3 × 105) (n = 134)7.0 ×106 (1.1 × 106–1.0 × 107) (n = 137)
rs1024611NSNS
A/GG45 (24.46)1.0 × 104 (1.6 × 103–4.9 × 104) (n = 44)9.2 ×106 (8.4 × 105–1.0 × 107) (n = 43)
DC-SIGNG107 (58.15)1.1 × 104 (2.0 × 103–1.3 × 105) (n = 101)9.6 ×106 (1.3 × 106–1.0 × 107) (n = 106)
rs735240NSNS
A/GA77 (41.85)9.4 × 103 (2.1 × 103–5.7 × 104)6.1 ×106 (1.0 × 106–1.0 × 107) (n = 74)
TLR2G174 (94.57)1.1 × 104 (2.1 × 103–1.0 × 105) (n = 168)8.6 ×106 (1.1 × 106–1.0 × 107) (n = 170)
rs5743708NSNS
A/GA10 (5.43)4.3 × 103 (1.6 × 103–3.8 × 104)1.0 ×107 (1.0 × 106–1.0 × 107)
TLR4C175 (95.11)1.0 × 104 (2.1 × 103–9.8 × 104) (n = 169)8.6 ×106 (1.1 × 106–1.0 × 107) (n = 171)
rs4986791NSNS
C/TT9 (4.89)2.0 × 104 (2.8 × 103–9.8 × 104)1.0 ×107 (1.7 × 106–1.0 × 107)
TLR9T107 (58.15)1.7 × 103 (2.1 × 103–1.5 × 105) (n = 103)9.2 ×106 (1.1 × 106–1.0 × 107) (n = 104)
rs352140NSNS
C/TC77 (41.85)7.9 × 103 (1.7 × 103–5.1 × 104) (n = 75)7.8 ×106 (1.0 × 106–1.0 × 107) (n = 76)

Data are presented as median (IQR- interquartile range) or number (%).

cCMV, congenital cytomegalovirus; CCL2,C-C motif chemokine ligand 2; DC-SIGN, dendritic cell-specific ICAM-grabbing non-integrin; HCMV, human cytomega

lovirus; IL, interleukin; NS, not significant (p < 0.05); SNP, single nucleotide polymorphism;; TLR, toll-like receptor.

a SNP database (dbSNP) reference number (ID number).

b p-value – for comparison between alleles and viremia.

c p-value – for comparison between alleles and viruria.

Table S7

Association between alleles of examined polymorphisms (SNPs) and viremia and viruria in asymptomatic newborn infants with cCMV infection

SNP, rs numbera, allelesAllelen, (%)HCMV DNA (copies/mL) in bloodp-valuebHCMV DNA (copies/mL) in urinep-valuec
IL1BG24 (63.16)2.0 × 103 (7.5 × 102–3.3 × 103) (n = 20)4.9 ×105 (1.4 × 105–5.3 × 106)
rs16944NSNS
G/AA14 (36.84)1.8 × 103 (9.9 × 102–2.7 × 104)2.4 ×106 (1.7 × 105–6.1 × 106)
IL12BT32 (84.21)1.8 × 103 (9.9 × 102–1.5 × 104) (n = 28)6.9 ×105 (1.4 × 105–5.3 × 106)
rs3212227NSNS
G/TG6 (15.79)2.1 × 103 (0.0–4.0 × 103)1.0 ×106 (1.7 × 105–2.0 × 107)
IL28BC28 (73.68)2.1 × 103 (6.5 × 102–2.7 × 104) (n = 24)1.3 ×106 (9.1 × 104–6.1 × 106)
rs12979860NSNS
C/TT10 (26.32)1.2 × 103 (9.9 × 102–2.7 × 103)2.9 ×105 (2.5 × 105–2.8 × 106)
CCL2A29 (76.32)1.8 × 103 (9.9 × 102–4.0 × 103) (n = 26)6.9 ×105 (1.7 × 105–6.1 × 106)
rs1024611NSNS
A/GG9 (23.68)2.4 × 103 (9.5 × 102–1.5 × 104) (n = 8)2.5 ×105 (1.4 × 105–3.2 × 106)
DC-SIGNG20 (52.63)1.2 × 103 (1.5 × 102–3.0 × 103) (n = 16)4.9 ×105 (1.4 × 105–7.5 × 106)
rs735240NSNS
A/GA18 (47.37)2.1 × 103 (1.2 × 103–3.2 × 104)1.3 ×106 (1.7 × 105–4.6 × 106)
TLR2G36 (94.74)2.0 × 103 (6.5 × 102–1.5 × 104) (n = 32)1.3 ×106 (1.4 × 105–6.1 × 106)
rs5743708NSNS
A/GA2 (5.26)1.4 × 103 (1.2 × 103–1.6 × 103)2.3 ×105 (1.7 × 105–2.9 × 105)
TLR4C36 (94.74)2.0 × 103 (9.9 × 102–1.5 × 104) (n = 32)6.9 ×105 (1.5 × 105–5.3 × 106)
rs4986791NSNS
C/TT2 (5.26)2.0 × 103 (0–4.0 × 103)1.0 ×107 (0–2.0 × 107)
TLR9T23 (60.53)1.8 × 103 (1.0 × 103–4.0 × 103) (n = 20)2.9 ×105 (1.4 × 105–6.1 × 106)
rs352140NSNS
C/TC15 (39.47)2.0 × 103 (3.1 × 102–2.7 × 104) (n = 14)2.8 ×106 (4.0 × 104–6.1 × 106)

Data are presented as median (IQR- interquartile range) or number (%).

cCMV, congenital cytomegalovirus; CCL2, C-C motif chemokine ligand 2; DC-SIGN, dendritic cell-specific ICAM-grabbing non-integrin; HCMV, human cytomega lovirus; IL, interleukin; NS, not significant (p < 0.05); SNP, single nucleotide polymorphism; TLR, toll-like receptor.

a SNP database (dbSNP) reference number (ID number).

b p-value – for comparison between alleles and viremia.

c p-value – for comparison between alleles and viruria.

DOI: https://doi.org/10.34763/jmotherandchild.20202404.d-20-00014 | Journal eISSN: 2719-535X | Journal ISSN: 2719-6488
Language: English
Page range: 9 - 17
Published on: Jul 16, 2021
Published by: Institute of Mother and Child
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year

© 2021 Dominika Jedlińska-Pijanowska, Beata Kasztelewicz, Anna Dobrzańska, Katarzyna Dzierżanowska-Fangrat, Maciej Jaworski, Justyna Czech-Kowalska, published by Institute of Mother and Child
This work is licensed under the Creative Commons Attribution 4.0 License.