Table 6.

Summary of genetic variables selected by LASSO multivariate analysis and their influence on GVHD/NRM development compared with previous publications

Genetic variablePolymorphismGenotypeD/ROR*InflammatoryPhysiologyReference
aGVHD 2-4aGVHD 3-4cGVHDExtensive cGVHDNRM
IL-1A rs1800587 TT R  H   H Pro T/T genotype: increased promoter activity and IL-1A production, higher incidence of cGVHD 51,52  
IL-1B rs1143627 TT R L     Pro C allele: high levels of IL-1 53  
  CC<CT<TT D   H H   TT: higher risk of aGVHD 54  
 rs16944 CC R L      T allele: high levels of IL-1 53  
  TT<TC<CC D  H       
 rs1143634 TT<CT<CC R  L  H   T allele: high IL-1 production and more aGVHD; TT genotype: correlated with protector for infections 55,-57  
  TT D  H†  H L    
IL-2 rs2069762 GT D     H Pro GG: lower levels of IL-2 and lower GVHD 58,59  
  GG R  L† L H L    
  GT R  H H   
IL-6 rs1800795 GG/GC R  H    Pro Allele G: higher levels of IL-6, higher risk of aGVHD 60,61  
  GG D  L      
IL-7R rs1494555 GG R  H†    Pro GG in donor: higher severe GVHD and NRM 62  
  GA D  L  H L 
IL-10 rs1800871 TC R  H†    Anti Allele C: high IL-10 production, Lower GVHD 63,64  
  TT/TC D H      
 rs1800872 AC R  H     Allele C: high IL-10 production, lower GVHD  
 rs1800896 AG R H      Allele G: high IL-10 production, lower GVHD  
  AG D H        
IL-17A rs8193036 CC R  H H   Pro Genotype CC: higher GVHD 38  
  CC D H H†       
  CT D  L       
 rs2275913 AA R  L†   H  Allele A: correlated with higher levels of IL-17A and higher GVHD in donor 65,66  
 AA D  H    
  AG D  L       
 rs3819024 GG R  L     Allele A: correlated with lower levels of IL-17A and lower GVHD  
  GG D H H       
 rs4711998 GG/AG R    H    
  AA<AG<GG D  L       
IL-23R rs6687620 TT<CT<CC R   L   Pro   
  CT R     H    
  TT R  L  H†     
  TT/CT D  L†  L     
 rs11209026 GG R   L    No correlation was obtained 67  
IFN-γ rs2430561 AT R    L  Pro/anti Genotype TT: correlated with higher levels; T allele: correlated with moderate-severe GVHD 68,69  
  TT R     L    
  AA R  H       
  AT D  L       
 rs2069705 TT<CT<CC R  L     Genotype TT: correlated with higher levels; CC genotype: correlated with low incidence of cGVHD 70,71  
  CC D L        
  CT/TT D  H  H H    
TGFβ rs2241716 GG D L† L†    Anti Genotype AA: high incidence of extensive cGVHD 71  
 rs1800469 CC R L      Allele C: correlated with higher probability to develop aGVHD and lower levels 71,72  
  CT D H        
  TT D   L L     
TNFα rs1799964 CC R L     Pro TT carriers: lower levels than CC genotype 73,74  
  CC D  H       
 rs1800629 AG R  H†     AA genotype: correlated with higher levels 75,76  
 rs361525 AG R  H     GG genotype: low production of TNFα; GA genotype: higher rates of cGVHD 77,78  
  GG D   L      
Genetic variablePolymorphismGenotypeD/ROR*InflammatoryPhysiologyReference
aGVHD 2-4aGVHD 3-4cGVHDExtensive cGVHDNRM
IL-1A rs1800587 TT R  H   H Pro T/T genotype: increased promoter activity and IL-1A production, higher incidence of cGVHD 51,52  
IL-1B rs1143627 TT R L     Pro C allele: high levels of IL-1 53  
  CC<CT<TT D   H H   TT: higher risk of aGVHD 54  
 rs16944 CC R L      T allele: high levels of IL-1 53  
  TT<TC<CC D  H       
 rs1143634 TT<CT<CC R  L  H   T allele: high IL-1 production and more aGVHD; TT genotype: correlated with protector for infections 55,-57  
  TT D  H†  H L    
IL-2 rs2069762 GT D     H Pro GG: lower levels of IL-2 and lower GVHD 58,59  
  GG R  L† L H L    
  GT R  H H   
IL-6 rs1800795 GG/GC R  H    Pro Allele G: higher levels of IL-6, higher risk of aGVHD 60,61  
  GG D  L      
IL-7R rs1494555 GG R  H†    Pro GG in donor: higher severe GVHD and NRM 62  
  GA D  L  H L 
IL-10 rs1800871 TC R  H†    Anti Allele C: high IL-10 production, Lower GVHD 63,64  
  TT/TC D H      
 rs1800872 AC R  H     Allele C: high IL-10 production, lower GVHD  
 rs1800896 AG R H      Allele G: high IL-10 production, lower GVHD  
  AG D H        
IL-17A rs8193036 CC R  H H   Pro Genotype CC: higher GVHD 38  
  CC D H H†       
  CT D  L       
 rs2275913 AA R  L†   H  Allele A: correlated with higher levels of IL-17A and higher GVHD in donor 65,66  
 AA D  H    
  AG D  L       
 rs3819024 GG R  L     Allele A: correlated with lower levels of IL-17A and lower GVHD  
  GG D H H       
 rs4711998 GG/AG R    H    
  AA<AG<GG D  L       
IL-23R rs6687620 TT<CT<CC R   L   Pro   
  CT R     H    
  TT R  L  H†     
  TT/CT D  L†  L     
 rs11209026 GG R   L    No correlation was obtained 67  
IFN-γ rs2430561 AT R    L  Pro/anti Genotype TT: correlated with higher levels; T allele: correlated with moderate-severe GVHD 68,69  
  TT R     L    
  AA R  H       
  AT D  L       
 rs2069705 TT<CT<CC R  L     Genotype TT: correlated with higher levels; CC genotype: correlated with low incidence of cGVHD 70,71  
  CC D L        
  CT/TT D  H  H H    
TGFβ rs2241716 GG D L† L†    Anti Genotype AA: high incidence of extensive cGVHD 71  
 rs1800469 CC R L      Allele C: correlated with higher probability to develop aGVHD and lower levels 71,72  
  CT D H        
  TT D   L L     
TNFα rs1799964 CC R L     Pro TT carriers: lower levels than CC genotype 73,74  
  CC D  H       
 rs1800629 AG R  H†     AA genotype: correlated with higher levels 75,76  
 rs361525 AG R  H     GG genotype: low production of TNFα; GA genotype: higher rates of cGVHD 77,78  
  GG D   L      
*

OR values for the variables selected by the LASSO procedure (described in “Methods”). OR values were obtained with the exponential function of β coefficient, which compares the strength of the effect of each individual independent variable with the dependent variable. The higher the absolute value of β, the stronger the effect. β = 0, OR = 1 (neutral); β < 0, OR < 1 (L); β > 0, OR > 1 (H).

†

H, OR > 2; L, OR < 0.5.

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