Table III.
Candidate SNP (rs9916629) and secondary outcome of NK cell functional response following stimulation
| Condition | Variable | Median Percentage of Expression (Quartile 1–Quartile 3) |
Unadjusted |
Multivariatea |
||||
|---|---|---|---|---|---|---|---|---|
| CC (n = 8) | CT (n = 43) | TT (n = 45) | Direction of Effect |
p | Direction of Effect |
p | ||
| 721.221 | CD107a/NK | 11.18 (9.02–14.9) | 9.72 (7–14.9) | 8.04 (5.7–10.4) | ↑ | 0.021 | ↑ | 0.017 |
| 721.221 | IFN-γ/NK | 3.76 (2.6–7.7) | 3.2 (1.62–5.07) | 3.38 (2.19–4.89) | ↑ | 0.76 | ↑ | 0.82 |
| 721.221 | MIP-1β/NK | 30.8 (28.7–41.8) | 31.1 (22.5–42.3) | 37.15 (31.25–41.95) | ↓ | 0.062 | ↓ | 0.11 |
| 721.221 | CD107a/CD56bright | 10.12 (8.3–15.7) | 9.83 (5.64–14.3) | 6.5 (4.45–10.6) | ↑ | 0.02 | ↑ | 0.023 |
| 721.221 | IFN-γ/CD56bright | 1.44 (0.87–3.14) | 1.32 (0.71–2.66) | 1.5 (1–2.62) | ↓ | 0.89 | ↓ | 0.84 |
| 721.221 | MIP-1β/CD56bright | 15.7 (9.26–27.7) | 15.7 (12.25–22.55) | 15.6 (11.2–25.25) | ↓ | 0.63 | ↓ | 0.77 |
| 721.221 | CD107a/CD56dim | 12.2 (7.95–14.6) | 9.72 (6.97–14.5) | 7.68 (5.47–9.92) | ↑ | 0.021 | ↑ | 0.018 |
| 721.221 | IFN-γ/CD56dim | 4.8 (2.98–8.82) | 3.39 (1.88–5.39) | 3.59 (2.29–5.44) | ↑ | 0.58 | ↑ | 0.63 |
| 721.221 | MIP-1β/CD56dim | 38.8 (32.4–47.2) | 38.2 (28.6–46.9) | 41.6 (34.1–48.35) | ↓ | 0.18 | ↓ | 0.24 |
| K562 | CD107a/NK | 25.55 (23.15–34.65) | 26.2 (20.9–33.9) | 25.1 (16.6–30.7) | ↑ | 0.092 | ↑ | 0.06 |
| K562 | IFN-γ/NK | 5.31 (2.42–8.3) | 3.83 (2.84–6.02) | 4.34 (2.65–7.02) | ↑ | 0.77 | ↑ | 0.72 |
| K562 | MIP-1β/NK | 44.4 (40.5–48.9) | 43.1 (35.1–51.3) | 47.3 (39.85–56.25) | ↓ | 0.039 | ↓ | 0.10 |
| K562 | CD107a/CD56bright | 22.65 (15.35–28.15) | 20 (12–27.7) | 16.8 (13.3–23.6) | ↑ | 0.18 | ↑ | 0.17 |
| K562 | IFN-γ/CD56bright | 1.21 (0.75–2.68) | 1.53 (0.84–2.04) | 1.49 (0.89–2.11) | ↓ | 0.92 | ↑ | 0.92 |
| K562 | MIP-1β/CD56bright | 16.6 (8.44–23.5) | 18.5 (14.5–22.3) | 18.75 (11.85–23.9) | ↓ | 0.48 | ↓ | 0.69 |
| K562 | CD107a/CD56dim | 26.7 (25.15–40.7) | 27.7 (21.6–35) | 26 (17.5–31) | ↑ | 0.081 | ↑ | 0.056 |
| K562 | IFN-γ/CD56dim | 6.1 (3.27–10.11) | 4.48 (3.35–6.49) | 5.03 (2.86–7.57) | ↑ | 0.45 | ↑ | 0.41 |
| K562 | MIP-1β/CD56dim | 51.7 (45.7–59.9) | 53 (41.9–57.2) | 52.3 (42.35–62.6) | ↓ | 0.31 | ↓ | 0.53 |
| 815AB | CD107a/NK | 37.1 (25.5–42.65) | 36.5 (30.4–42.9) | 33.1 (24.9–42.1) | ↑ | 0.64 | ↑ | 0.48 |
| 815AB | IFN-γ/NK | 7.09 (5.65–10.54) | 5.5 (3.61–7.88) | 7.73 (4.21–10.84) | ↓ | 0.44 | ↓ | 0.57 |
| 815AB | MIP-1β/NK | 67.6 (59.1–78.6) | 72.4 (60–79.9) | 80.8 (72.95–85.4) | ↓ | 0.016 | ↓ | 0.039 |
| 815AB | CD107a/CD56bright | 18.6 (10.16–27.65) | 18.3 (11.7–25.7) | 15 (9.27–20.6) | ↑ | 0.5 | ↑ | 0.48 |
| 815AB | IFN-γ/CD56bright | 1.37 (1.24–2.62) | 1.34 (0.66–2.11) | 1.61 (0.86–2.15) | ↑ | 0.82 | ↑ | 0.84 |
| 815AB | MIP-1β/CD56bright | 26.2 (10.7–29.2) | 19.5 (13.4–26.1) | 20.55 (14.8–28) | ↓ | 0.49 | ↓ | 0.67 |
| 815AB | CD107a/CD56dim | 42.55 (30.25–46.4) | 38.6 (32.4–45.1) | 33.7 (25.8–44.1) | ↑ | 0.44 | ↑ | 0.34 |
| 815AB | IFN-γ/CD56dim | 9.8 (6.61–14.4) | 7.22 (5.41–10.1) | 9.41 (5.19–12.3) | ↑ | 0.89 | ↑ | 0.82 |
| 815AB | MIP-1β/CD56dim | 77.4 (72–90.7) | 84.7 (76.5–87.8) | 86.75 (79.85–90.15) | ↓ | 0.19 | ↓ | 0.3 |
| PMA | CD107a/NK | 33.45 (13.7–48.35) | 13.9 (8.39–28.3) | 10.3 (5.88–15.3) | ↑ | 0.0014 | ↑ | 0.0011 |
| PMA | IFN-γ/NK | 23.45 (15.8–38.9) | 9.95 (5.11–18.1) | 9.59 (3.41–18.7) | ↑ | 0.031 | ↑ | 0.054 |
| PMA | MIP-1β/NK | 75.1 (64.3–81.7) | 55.6 (47–65.2) | 58.85 (34.65–73.9) | ↑ | 0.38 | ↑ | 0.44 |
| PMA | CD107a/CD56bright | 59.35 (30.35–75.95) | 36.5 (20.9–61.3) | 24.5 (15.4–42.3) | ↑ | 0.0055 | ↑ | 0.007 |
| PMA | IFN-γ/CD56bright | 26.15 (21.35–52.35) | 20.2 (9.15–29.5) | 16.3 (10.8–26.4) | ↑ | 0.04 | ↑ | 0.056 |
| PMA | MIP-1β/CD56bright | 82.9 (80.6–93.6) | 72.7 (63–81.8) | 74.05 (60.5–85) | ↑ | 0.46 | ↑ | 0.4 |
| PMA | CD107a/CD56dim | 19.6 (8.46–35.4) | 9.85 (4.63–16.7) | 5.72 (3.78–10.7) | ↑ | 0.0096 | ↑ | 0.0098 |
| PMA | IFN-γ/CD56dim | 23.9 (11.65–30.7) | 7.99 (2.8–15.4) | 7.81 (2.42–18.4) | ↑ | 0.1 | ↑ | 0.17 |
| PMA | MIP-1β/CD56dim | 69.4 (60.5–80.3) | 61.5 (43.3–72.5) | 62.55 (29.25–77.05) | ↑ | 0.27 | ↑ | 0.34 |
Genotype and quantitative trait association were analyzed using PLINK with the C allele of rs9916629 as the reference allele. Direction of effect is relative to the C allele and is determined from the beta value. In the multivariate analysis, association between rs9916629 and the phenotype was further adjusted for age and sex as covariates. Boldface indicates a p value meeting a Bonferroni-corrected threshold for multiple comparisons. 721.221, HLA class I-deficient B cell line; 815AB, p815 Ab (a mouse leukemic cell line coated with specific Ab; Ab-dependent cell-mediated cytotoxicity); CD107a, marker of degranulation; IFN-γ, IFN-γ–secreting NK cells; K562, MHC-devoid target cell line; MIP-1β, macrophage inflammatory protein-1β–secreting NK; PMA, phorbol 12-myristate 13-acetate and ionomycin (positive control).
Outcomes were adjusted for the appropriate background (media alone or uncoated p815 cell line).