Table II.
Genetic polymorphisms influencing aGVHD risk.
| Gene | Polymorphism | Impact* | Study population (n) | Reference |
|---|---|---|---|---|
| IFNG | IFNG Intron genotype | NSA | Related (100) | (Socie, et al 2001) |
| Recipient IFNG Intron 3/3 | OR=3.9 [1.2–12.4] | Related (80) | (Cavet, et al 2001) | |
| ↑ aGVHD | Related(88) | (Middleton, et al 2002) | ||
| Recipient IFNG Intron 2/2 | OR=0.2 [0.05–0.99] | Related (110) | (Mlynarczewska, et al 2004) | |
|
| ||||
| IL1A | −889(C/T) | NSA | Unrelated (90) | (MacMillan, et al 2003) |
| NSA | Unrelated (426) | (Mehta, et al 2007) | ||
|
| ||||
| IL1RN | IL1RN*2 | NSA | Related (570) | (Lin, et al 2003) |
| NSA | Unrelated (90) | (MacMillan, et al 2003) | ||
| Absence of donor IL1RN*2 | OR=6.2 | Related (99) | (Cullup, et al 2001) | |
| HR=2.1 [1.1–3.9] | Related (107) | (Rocha, et al 2002) | ||
|
| ||||
| IL1B | −511(C/T) | NSA | Related (570) | (Lin, et al 2003) |
| NSA | Unrelated (90) | (MacMillan, et al 2003) | ||
| +3953(C/T) | NSA | Related (77) | (Bertinetto, et al 2006) | |
| +3954(C/T) | NSA | Related (570) | (Lin, et al 2003) | |
|
| ||||
| IL6 | −174(C/G) | NSA | Related (570) | (Lin, et al 2003) |
| Recipient −174(G/G) | HR=4.1 | Related (108) | (Middleton, et al 2003) | |
| OR=2.2 [1.1–4.5] | Related, Unrelated (166) | (Ambruzova, et al 2009) | ||
| Donor −174(G/*) | HR=4.3 [1.5–12.1] | Related (160) | (Mullighan, et al 2004) | |
| Donor −174(G/G) | OR=3.9 [1.1–14.0] | Related (93) | (Karabon, et al 2005) | |
|
| ||||
| IL10 | −1064: Increased dinucleotide repeats (Alleles 12–15) | |||
| Recipient with Alleles 12–15 | OR=4.6 [1.2–17.8] | Related (80) | (Cavet, et al 2001) | |
| ↑ aGVHD | Related (88) | (Middleton, et al 2002) | ||
| Recipient homozygous for allele 13 | ↑ aGVHD | Related, Unrelated (196) | (Nordlander, et al 2002) | |
| −1082(A/G), −819(C/T), −592(A/C) Haplotype | NSA | Related (160) | (Mullighan, et al 2004) | |
| Recipient (GCC/GCC) | OR=0.09 [0.01–0.96] | Related (93) | (Karabon, et al 2005) | |
| HR=0.2 [0.06–0.7] (severe GVHD) | Related; Paediatric (57) | (Goussetis, et al 2011) | ||
| RR=7.9 [2.9–21.5] | Related (100) | (Socie, et al 2001) | ||
| Donor (GCC/GCC) | RR=0.3 [0.1–0.8] | Related (100) | (Socie, et al 2001) | |
| Absence of both donor and recipient (GCC) | OR=2.9 [1.1–7.7] | Related (77) | (Bertinetto, et al 2006) | |
|
| ||||
| IL23R | 1142A>G | |||
| Donor 1142(G/*) | RR=0.5 [0.3–0.97] | Related, Unrelated (407) | (Elmaagacli, et al 2008) | |
| ↓ aGVHD | Related, Unrelated, Haplo-identical; Paediatric (231) | (Gruhn, et al 2009) | ||
| OR=0.4 [0.2–0.95] | Related, Unrelated (304) | (Wermke, et al 2010) | ||
| variant SNPs | NSA [0.5–2.3] | Unrelated (390) | (Nguyen, et al 2010) | |
|
| ||||
| NOD2 | SNPs 8,12,13 | NSA | Related, Unrelated (198) | (Sairafi, et al 2008) |
| NSA | Related, Unrelated, Haplo-identical; Paediatric (231) | (Gruhn, et al 2009) | ||
| NSA [0.6–2.3] | Unrelated (390) | (Nguyen, et al 2010) | ||
| NSA [0.4–1.5] | Related, Unrelated (304) | (Wermke, et al 2010) | ||
| Donor only SNPs | RR=0.003 [0.002–0.007] (severe GVHD) | Related, Unrelated (403) | (Elmaagacli, et al 2006) | |
| Simultaneous SNPs in donor and recipient: | RR=4.3 [2.1–9.3] (severe GVHD) | Related, Unrelated (403) | (Elmaagacli, et al 2006) | |
| 1+ variant in either donor or recipient | ↑ aGVHD | Related, Unrelated (700) | (Holler, et al 2008) | |
| Donor SNP13 | ↑ aGVHD (unrelated only) | Related, Unrelated (700) | (Holler, et al 2008) | |
|
| ||||
| TNF | TNFd3 | NSA | Related (100) | (Socie, et al 2001) |
| NSA | Related, Unrelated (196) | (Nordlander, et al 2002) | ||
| NSA | Unrelated, Paediatric (180) | (Goyal, et al 2010) | ||
| Recipient TNF d3/d3 | ↑ aGVHD | Related (49) | (Middleton, et al 1998) | |
| OR=3.3 [1.1–10.2] | Related (80) | (Cavet, et al 2001) | ||
| TNFd4 | ||||
| Recipient TNF d4/d4 | HR=2.3 (severe GVHD) | Unrelated, Paediatric (180) | (Goyal, et al 2010) | |
| Recipient TNFd4 | 4.3 [1.3–14.6] (related only) | Related, Unrelated (196) | (Nordlander, et al 2002) | |
| −308(A/G) | NSA | Related (100) | (Socie, et al 2001) | |
| NSA | Related (107) | (Rocha, et al 2002) | ||
| NSA | Related, Unrelated (196) | (Nordlander, et al 2002) | ||
| NSA | Related (570) | (Lin, et al 2003) | ||
| NSA | Related (49) | (Middleton, et al 1998) | ||
|
| ||||
| VDR | ApaI(A/a) | |||
| Recipient ApaI(a/*) | ↑ aGVHD | Related (88) | (Middleton, et al 2002) | |
| Donor ApaI(A/A) | OR=7.2 [1.6–32.1] | Related, Unrelated, Haplo-identical (123) | (Bogunia-Kubik, et al 2008) | |
| Taql(T/t) | ||||
| Recipient TaqI(T/*) | HR=2.6 [1.2–5.6] (severe GVHD) | Related (107) | (Rocha, et al 2009) | |
| FokI(F/f) | ||||
| Donor FokI(F/F) | OR=4.5 [1.2–16.5] | Related, Unrelated, Haplo-identical (123) | (Bogunia-Kubik, et al 2008) | |
*
Relative risk (RR), hazard ratio (HR) or odds ratio (OR) provided when reported, otherwise increased or decreased risk is reported. Confidence intervals, when provided, are in brackets.
aGVHD - acute graft-versus-host disease; NSA – No significant association; SNP – Single nucleotide polymorphism; RR – Relative risk; HR – Hazard ratio; OR – Odds ratio