Table 5.
Associations between SNPs in CD46, SLAM and CD209 genes and secreted cytokine immune responses to measles vaccine in the combined, Caucasian and African-American study subjects
| Secreted cytokine/Gene | SNPID | Location/function | Genotyp ea | n | Median, pg/ml (IQR)b | p valuec |
|---|---|---|---|---|---|---|
| IL-2 | ||||||
| Combined cohort of subjects (n = 745) | ||||||
| None | ||||||
| Caucasian subgroup fn = 598) | ||||||
| SLAM | rs2295614 | flanking 5′ UTR | TT | 514 | 42.4 (23.3; 66.8) | 0.0303 |
| TA | 76 | 34.4 (19.0; 65.9) | ||||
| AA | 2 | 31.5 (17.7; 45.3) | ||||
| African-American subgroup (n = 89) | ||||||
| CD46 | rs2724382 | intron | GG | 33 | 28.9 (16.8; 67.6) | 0.0117 |
| GC | 44 | 31.1 (15.3; 46.4) | ||||
| CC | 11 | 15.2 (8.4; 36.6) | ||||
| CD209 | rs8112310 | flanking 3′ UTR | TT | 24 | 25.3 (11.8; 48.6) | 0.0170 |
| TA | 62 | 30.1 (15.6; 52.8) | ||||
| AA | 0 | – | ||||
| CD46 | rs2796268 | flanking 5′ UTR | AA | 28 | 32.8 (15.3; 82.1) | 0.0282 |
| AG | 45 | 30.6 (17.2; 43.4) | ||||
| GG | 15 | 15.4 (11.3; 36.6) | ||||
| CD209 | rs4804806 | flanking 5′ UTR | GG | 33 | 36.6 (18.5; 59.2) | 0.0297 |
| GA | 37 | 22.7 (12.3; 50.6) | ||||
| AA | 18 | 29.0 (15.2; 35.1) | ||||
| CD46 | rs2724385 | intron | AA | 40 | 27.2 (13.9; 51.9) | 0.0331 |
| AT | 44 | 27.9 (15.9; 46.4) | ||||
| TT | 4 | 44.1 (33.8; 75.2) | ||||
| SLAM | rs3766362 | intron | AA | 30 | 15.7 (11.3; 46.6) | 0.0381 |
| AT | 38 | 29.0 (17.0; 52.8) | ||||
| TT | 20 | 36.7 (22.8; 47.7) | ||||
| SLAM | rs6704124 | intron | GG | 52 | 25.6 (12.2; 43.2) | 0.0412 |
| GA | 30 | 29.8 (17.0; 52.8) | ||||
| AA | 6 | 43.6 (18.5; 65.6) | ||||
| IL-6 | ||||||
| Combined cohort of subjects (n = 745) | ||||||
| CD46 | rs2796267 | flanking 5′ UTR | AA | 270 | 359.3 (257.6; 479.8) | 0.0006 |
| AG | 343 | 353.8 (236.4; 458.3) | ||||
| GG | 123 | 341.2 (245.2; 446.9) | ||||
| CD46 | rsllll8516 | intron | GG | 640 | 361.2 (253.7; 469.7) | 0.0133 |
| GA | 92 | 305.4 (206.7; 401.0) | ||||
| AA | 1 | 348.1 (348.1; 348.1) | ||||
| CD46 | rs2724384* | intron | AA | 447 | 348.4 (245.8; 458.0) | 0.0275 |
| AG | 260 | 365.5 (253.5; 470.1) | ||||
| GG | 30 | 381.6 (269.5; 498.4) | ||||
| CD46 | rs41316827 | intron | CC | 710 | 354.6 (248.4; 461.4) | 0.0493 |
| CA | 26 | 348.5 (221.0; 469.5) | ||||
| AA | 1 | 332.2 (332.2; 332.2) | ||||
| Caucasian subgroup (n = 598) | ||||||
| CD46 | rs2796267 | flanking 5′ UTR | AA | 203 | 356.2 (254.6; 469.5) | 0.0042 |
| AG | 281 | 351.3 (240.2; 457.6) | ||||
| GG | 107 | 351.5 (218.4; 454.9) | ||||
| African-American subgroup (n = 89) | ||||||
| CD46 | rsllll8516 | intron | GG | 75 | 348.9 (247.8; 462.4) | 0.0012 |
| GA | 13 | 295.5 (224.9; 303.5) | ||||
| AA | 0 | – | ||||
| CD46 | rs2796267 | flanking 5′ UTR | AA | 45 | 358.9 (287.6; 479.8) | 0.0180 |
| AG | 34 | 304.3 (230.9; 418.9) | ||||
| GG | 9 | 286.1 (269.5; 295.5) | ||||
| CD209 | rs4804806 | flanking 5′ UTR | GG | 33 | 364.9 (269.8; 480.9) | 0.0254 |
| GA | 37 | 318.4 (230.7; 399.8) | ||||
| AA | 18 | 321.9 (247.8; 436.0) | ||||
| SLAM | rs2753260 | intron | AA | 51 | 340.2 (262.5; 477.6) | 0.0313 |
| AC | 32 | 314.3 (227.8; 382.1) | ||||
| CC | 5 | 358.9 (238.7; 370.6) | ||||
| IL-10 | ||||||
| Combined cohort of subjects (n = 745) | ||||||
| None | ||||||
| Caucasian subgroup (n = 598) | ||||||
| CD209 | rsl2611071 | flanking 5′ UTR | CC | 452 | 17.8 (11.9; 28.2) | 0.0246 |
| CA | 129 | 19.8 (12.4; 30.2) | ||||
| AA | 13 | 21.4 (17.4; 29.6) | ||||
| African-American subgroup (n = 89) | ||||||
| SLAM | rsl 1265452* | intron | GG | 31 | 12.1 (7.4; 22.2) | 0.0008 |
| GA | 31 | 13.3 (7.4; 28.6) | ||||
| AA | 26 | 13.9 (7.9; 26.2) | ||||
| SLAM | rs2089088 | intron | AA | 66 | 10.9 (7.4; 20.6) | 0.0232 |
| AC | 18 | 22.2 (12.8; 35.0) | ||||
| CC | 4 | 16.4 (10.1; 31.2) | ||||
| IFN-α | ||||||
| Combined cohort of subjects (n = 745) | ||||||
| CD46 | rs2724384* | intron | AA | 445 | 506.4 (244.5; 935.1) | 0.0068 |
| AG | 259 | 618.9 (321.8; 1,197.4) | ||||
| GG | 30 | 657.3 (344.5; 1,338) | ||||
| CD46 | rs41318019 | flanking 3′ UTR | GG | 645 | 567.2 (273.4; 1,047.4) | 0.0330 |
| GC | 87 | 509.9 (272.8; 846.6) | ||||
| CC | 2 | 262.5 (1.5; 523.5) | ||||
| CD46 | rsllll8516 | intron | GG | 637 | 559.3 (275.2; 1,025.3) | 0.0401 |
| GA | 92 | 491.2 (244.3; 1,028.8) | ||||
| AA | 1 | 210.2 (210.2; 210.2) | ||||
| CD209 | rs7250738 | flanking 5′ UTR | AA | 677 | 550.2 (264.4; 1,018.0) | 0.0427 |
| AG | 51 | 581.5 (393.3; 1,245.8) | ||||
| GG | 6 | 876.2 (271.9; 1,678.0) | ||||
| Caucasian subgroup (n = 598) | ||||||
| CD46 | rs2724384* | intron | AA | 338 | 545.8 (242.1; 955.7) | 0.0016 |
| AG | 223 | 661.9 (332.6; 1,220.6) | ||||
| GG | 27 | 703.0 (243.5; 1,338) | ||||
| CD46 | rsllll8516 | intron | GG | 521 | 593.9 (290.4; 1,093.5) | 0.0072 |
| GA | 62 | 679.1 (281.6; 1,012) | ||||
| AA | 1 | 210.2 (210.2; 210.2) | ||||
| CD46 | rs2724382 | intron | GG | 201 | 459.1 (225.1; 941.9) | 0.0084 |
| GC | 272 | 638.6 (328.2; 1,091.2) | ||||
| CC | 115 | 678.9 (312.6; 1,186.3) | ||||
| CD46 | rs2796268 | flanking 5′ UTR | AA | 196 | 462.4 (223.5; 963.9) | 0.0133 |
| AG | 269 | 639.6 (329.6; 1,101.5) | ||||
| GG | 118 | 670.4 (295.4; 1,156.1) | ||||
| CD46 | rs2796267 | flanking 5′ UTR | AA | 201 | 480.7 (219.3; 919.6) | 0.0148 |
| AG | 279 | 639.6 (328.2; 1,093.5) | ||||
| GG | 107 | 722.0 (282.5; 1,230.1) | ||||
| CD46 | rs7144 | 3′ UTR | AA | 204 | 462.4 (223.5; 951.7) | 0.0185 |
| AG | 271 | 639.6 (328.2; 1,101.5) | ||||
| GG | 113 | 661.9 (312.6; 1,156.1) | ||||
| CD209 | rsl2611071 | flanking 5′ UTR | CC | 448 | 591.9 (269.4; 1,051.6) | 0.0288 |
| CA | 127 | 581.5 (324.6; 1,093.5) | ||||
| AA | 13 | 969.6 (839.4; 1,678.0) | ||||
| African-American subgroup (n = 89) | ||||||
| SLAM | rsl7385878 | flanking 3′ UTR | GG | 47 | 293.6 (199.1; 535.4) | 0.0163 |
| GA | 35 | 450.6 (212.2; 805.2) | ||||
| AA | 6 | 621.8 (515; 1,109.3) | ||||
| SLAM | rs2295614 | flanking 5′ UTR | TT | 79 | 400.1 (212.2; 608.7) | 0.0253 |
| TA | 8 | 437.0 (241.5; 722.8) | ||||
| AA | 1 | 1,571.2 (1,571.2; 1,571.2) | ||||
| CD209 | rs4804805 | flanking 5′ UTR | AA | 63 | 293.6 (195.1; 546.9) | 0.0260 |
| AG | 21 | 550.3 (430.5; 1,173.4) | ||||
| GG | 4 | 506.6 (301.7; 636.0) | ||||
| SLAM | rs5002947 | flanking 3′ UTR | GG | 35 | 293.6 (162.5; 608.7) | 0.0396 |
| GA | 45 | 400.1 (253.5; 580.9) | ||||
| AA | 8 | 621.8 (488.8; 1,141.3) | ||||
| CD46 | rs41317049 | intron | AA | 80 | 417.5 (243.5; 659.4) | 0.0480 |
| AC | 7 | 321.8 (202.2; 498.1) | ||||
| CC | 0 | – | ||||
| IFN-γ | ||||||
| Combined cohort of subjects (n = 745) | ||||||
| SLAM | rs2295614 | flanking 5′ UTR | TT | 628 | 68.7 (36.9; 120.5) | 0.0128 |
| TA | 101 | 58.9 (23.5; 118.2) | ||||
| AA | 5 | 70.4 (13.1; 75.9) | ||||
| CD46 | rs2796267 | flanking 5′ UTR | AA | 270 | 63.6 (35.2; 123.3) | 0.0174 |
| AG | 343 | 66.7 (32.4; 112.2) | ||||
| GG | 123 | 76.4 (40.7; 131.4) | ||||
| Caucasian subgroup (n = 598) | ||||||
| None | ||||||
| African-American subgroup (n = 89) | ||||||
| CD209 | rs4804806 | flanking 5′ UTR | GG | 33 | 62.2 (26.0; 109.2) | 0.0007 |
| GA | 37 | 53.4 (31.1; 75.4) | ||||
| AA | 18 | 49.6 (14.4; 136) | ||||
| CD46 | rs2796268 | flanking 5′ UTR | AA | 28 | 46.6 (29.1; 133.1) | 0.0012 |
| AG | 45 | 62.8 (42.5; 97.8) | ||||
| GG | 15 | 38.9 (6.4; 69.5) | ||||
| CD46 | rs2724382 | intron | GG | 33 | 48.2 (28.2; 115.4) | 0.0072 |
| GC | 44 | 62.0 (34.5; 97.2) | ||||
| CC | 11 | 56.0 (6.2; 135.3) | ||||
| SLAM | rs2295614 | flanking 5′ UTR | TT | 79 | 57.3 (25.5; 105.2) | 0.0158 |
| TA | 8 | 61.4 (47.8; 101.9) | ||||
| AA | 1 | 70.4 (70.4; 70.4) | ||||
| CD46 | rs2796267 | flanking 5′ UTR | AA | 45 | 60.1 (30.1; 115.4) | 0.0204 |
| AG | 34 | 61.5 (26.1; 96.7) | ||||
| GG | 9 | 50.5 (24.5; 59.0) | ||||
| CD46 | rs2724385 | intron | AA | 40 | 56.2 (17.6; 82.3) | 0.0358 |
| AT | 44 | 61.5 (39.4; 118.8) | ||||
| TT | 4 | 60.6 (13.6; 167.0) | ||||
| CD46 | rs!7006738 | intron | GG | 63 | 57.3 (26.0; 97.8) | 0.0473 |
| GA | 23 | 61.3 (28.2; 139.3) | ||||
| AA | 2 | 32.5 (3.5; 61.4) | ||||
| IFNλ-1 | ||||||
| Combined cohort of subjects (n = 745) | ||||||
| SLAM | rs2295614 | flanking 5′ UTR | TT | 629 | 33.1 (14.2; 72.4) | 0.0027 |
| TA | 101 | 39.9 (14.2; 87.5) | ||||
| AA | 5 | 51.5 (−2.8; 126.8) | ||||
| CD46 | rs2724382 | intron | GG | 266 | 32.0 (12.6; 69.6) | 0.0443 |
| GC | 341 | 33.3 (14.8; 73.5) | ||||
| CC | 131 | 40.3 (17.1; 86.7) | ||||
| Caucasian subgroup (n = 598) | ||||||
| CD209 | rsl2611071 | flanking 5′ UTR | CC | 452 | 37.5 (15.0; 73.1) | 0.0027 |
| CA | 127 | 44.5 (22.6; 85.7) | ||||
| AA | 13 | 73.0 (36.2; 137.7) | ||||
| SLAM | rs2295614 | flanking 5′ UTR | TT | 512 | 39.3 (17.0; 76.2) | 0.0083 |
| TA | 76 | 40.6 (16.8; 91.1) | ||||
| AA | 2 | 188.8 (51.5; 326.1) | ||||
| CD209 | rs7248637 | 3′ UTR | GG | 492 | 38.7 (16.5; 75.7) | 0.0465 |
| GA | 92 | 40.2 (21.3; 86.0) | ||||
| AA | 6 | 71.2 (61.2; 163.9) | ||||
| African-American subgroup (n = 89) | ||||||
| SLAM | rs!7385878 | flanking 3′ UTR | GG | 47 | 13.1 (3.0; 24.9) | 0.0198 |
| GA | 35 | 25.6 (−5.7; 48.8) | ||||
| AA | 6 | 42.0 (21.5; 64.3) | ||||
| TNF-α | ||||||
| Combined cohort of subjects (n = 745) | ||||||
| CD46 | rs2724384* | intron | AA | 444 | 13.0 (8.5; 18.5) | 0.0007 |
| AG | 258 | 14.6 (10.1; 18.8) | ||||
| GG | 30 | 16.8 (11.0; 22.9) | ||||
| CD46 | rs7144 | 3′ UTR | AA | 264 | 12.8 (8.4; 17.6) | 0.0020 |
| AG | 339 | 14.0 (9.3; 18.8) | ||||
| GG | 129 | 15.2 (10.7; 20.9) | ||||
| CD46 | rs2724385 | intron | AA | 192 | 14.0 (10.1; 20.3) | 0.0030 |
| AT | 357 | 14.1 (9.1; 18.8) | ||||
| TT | 182 | 12.9 (8.8; 16.9) | ||||
| CD46 | rs2796268 | flanking 5′ UTR | AA | 251 | 12.9 (8.3; 18.3) | 0.0048 |
| AG | 337 | 13.9 (9.4; 18.8) | ||||
| GG | 138 | 14.9 (10.5; 20.4) | ||||
| CD46 | rs2724382 | intron | GG | 263 | 12.9 (8.4; 17.9) | 0.0143 |
| GC | 340 | 14.0 (9.3; 18.8) | ||||
| CC | 129 | 15.0 (10.6; 20.4) | ||||
| Caucasian subgroup (n = 598) | ||||||
| CD46 | rs2724384* | intron | AA | 337 | 13.1 (8.9; 18.2) | 2.3104E−05 |
| AG | 223 | 15.2 (10.3; 18.9) | ||||
| GG | 27 | 17.6 (11.0; 22.9) | ||||
| CD46 | rs7144 | 3′ UTR | AA | 204 | 13.1 (8.6; 17.3) | 0.0003 |
| AG | 271 | 14.2 (9.7; 18.9) | ||||
| GG | 112 | 15.3 (10.8; 20.7) | ||||
| CD46 | rs2796268 | flanking 5′ UTR | AA | 196 | 12.9 (8.4; 17.4) | 0.0005 |
| AG | 269 | 14.2 (10.0; 18.8) | ||||
| GG | 117 | 15.3 (10.7; 20.4) | ||||
| CD46 | rs2724382 | intron | GG | 201 | 13.0 (8.5; 17.1) | 0.0013 |
| GC | 272 | 14.6 (10.0; 18.9) | ||||
| CC | 114 | 15.3 (10.7; 20.4) | ||||
| CD46 | rs2724385 | intron | TT | 145 | 15.0 (10.6; 20.9) | 0.0013 |
| TA | 283 | 14.7 (9.5; 18.8) | ||||
| AA | 158 | 12.9 (8.9; 16.5) | ||||
| CD46 | rs2796267 | flanking 5′ UTR | AA | 200 | 12.8 (8.9; 17.8) | 0.0135 |
| AG | 279 | 14.6 (10.2; 18.8) | ||||
| GG | 107 | 15.5 (9.8; 20.4) | ||||
| African-American subgroup (n = 89) | ||||||
| SLAM | rsl0489635 | intron | GG | 77 | 11.8 (7.7; 18.1) | 0.0115 |
| GA | 11 | 7.4 (1.5; 13.4) | ||||
| AA | 0 | – | ||||
| CD46 | rsllll8516 | intron | GG | 75 | 11.6 (6.4; 17.4) | 0.0135 |
| GA | 13 | 10.3 (8.0; 16.5) | ||||
| AA | 0 | – | ||||
| CD46 | rsl7006738 | intron | GG | 63 | 10.3 (5.7; 17.0) | 0.0215 |
| GA | 23 | 13.9 (8.7; 18.8) | ||||
| AA | 2 | 23.4 (10.1; 36.6) | ||||
| CD209 | rs2287886 | flanking 5′ UTR | GG | 41 | 12.3 (8.0; 17.4) | 0.0236 |
| GA | 40 | 11.7 (6.0; 17.9) | ||||
| AA | 7 | 9.1 (7.4; 13.4) | ||||
A = Adeninę; C = cytosine; G = guanine; T = thymine; IQR = interquartile range.
A total of 55 SNPs were examined; only those found to be statistically significant (p ≤ 0.05) were included in the table. SNP rs8112310 (p = 1.1972E−07) displayed violations of HWE.
Values are presented as homozygous major allele/heterozygous/homozygous minor allele.
Values are median levels (IQR) in pg/ml as measured by ELISA.
Test for trend p value from the analysis of covariance adjusting for age, gender, race and age of immunization. The p values are adjusted for age, gender, race (when necessary), age at the first and second MMR and cohort status (cohort 1 vs. cohort 2) using analysis of covariance methodology.
Previously reported SNP associated with measles antibodies [24],