Associations of interactions between NLRP3 SNPs and HLA mismatch with acute and extensive chronic graft-versus-host diseases View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-10-12

AUTHORS

Hidekazu Takahashi, Naoko Okayama, Natsu Yamaguchi, Yuta Miyahara, Yasuo Morishima, Yutaka Suehiro, Takahiro Yamasaki, Koji Tamada, Satoshi Takahashi, Arinobu Tojo, Shigetaka Asano, Tsuyoshi Tanabe

ABSTRACT

HLA matching is a well-known genetic requirement for successful bone marrow transplantation (BMT). However, the importance of non-HLA single-nucleotide polymorphisms (SNPs) remains poorly understood. The NLR family pyrin domain–containing 3 (NLRP3) inflammasome, a key regulator of innate immunity, is associated with multiple diseases. We retrospectively genotyped SNPs of NLRP1–3 and caspase recruitment domain family member 8 (CARD8), which are implicated in the interleukin 1β (IL-1β) signaling, in 999 unrelated BMT donor–recipient pairs. We identified an association of the interaction between the recipient NLRP3 SNP CC genotype and total HLA mismatches with grade 2–4 acute graft-versus-host disease (AGVHD), and an association of the interaction between the donor NLRP3 SNP T allele and HLA-C mismatch with extensive chronic GVHD (ECGVHD), in both adjusted and unadjusted regressions (P < 0.005). Importantly, the ECGVHD risk associated with HLA-C mismatch was not elevated when the donor NLRP3 genotype was CC. We also identified an association of the interaction between recipient NLRP3 SNP and donor cytomegalovirus seropositivity with overall survival in adjusted regressions (P < 0.005). These results suggest the importance of certain SNP–covariate interactions in unrelated BMT. The three identified interactions may be useful for donor selection or outcome prediction. More... »

PAGES

13097

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-13506-w

DOI

http://dx.doi.org/10.1038/s41598-017-13506-w

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1092119444

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29026154


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29 schema:description HLA matching is a well-known genetic requirement for successful bone marrow transplantation (BMT). However, the importance of non-HLA single-nucleotide polymorphisms (SNPs) remains poorly understood. The NLR family pyrin domain–containing 3 (NLRP3) inflammasome, a key regulator of innate immunity, is associated with multiple diseases. We retrospectively genotyped SNPs of NLRP1–3 and caspase recruitment domain family member 8 (CARD8), which are implicated in the interleukin 1β (IL-1β) signaling, in 999 unrelated BMT donor–recipient pairs. We identified an association of the interaction between the recipient NLRP3 SNP CC genotype and total HLA mismatches with grade 2–4 acute graft-versus-host disease (AGVHD), and an association of the interaction between the donor NLRP3 SNP T allele and HLA-C mismatch with extensive chronic GVHD (ECGVHD), in both adjusted and unadjusted regressions (P < 0.005). Importantly, the ECGVHD risk associated with HLA-C mismatch was not elevated when the donor NLRP3 genotype was CC. We also identified an association of the interaction between recipient NLRP3 SNP and donor cytomegalovirus seropositivity with overall survival in adjusted regressions (P < 0.005). These results suggest the importance of certain SNP–covariate interactions in unrelated BMT. The three identified interactions may be useful for donor selection or outcome prediction.
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36 CC genotype
37 GVHD
38 HLA matching
39 HLA mismatches
40 HLA-C mismatches
41 NLR family pyrin
42 NLRP3 genotypes
43 NLRP3 single nucleotide polymorphisms
44 T allele
45 acute graft
46 alleles
47 association
48 association of interaction
49 bone marrow transplantation
50 chronic GVHD
51 chronic graft
52 cytomegalovirus seropositivity
53 disease
54 donor selection
55 donor-recipient pairs
56 extensive chronic GVHD
57 extensive chronic graft
58 family pyrin
59 genetic requirements
60 genotypes
61 grade 2
62 graft
63 host disease
64 immunity
65 importance
66 inflammasome
67 innate immunity
68 interaction
69 interleukin
70 key regulator
71 marrow transplantation
72 matching
73 member 8
74 mismatch
75 multiple diseases
76 non-HLA single nucleotide polymorphisms
77 outcome prediction
78 overall survival
79 pairs
80 polymorphism
81 prediction
82 pyrin
83 regression
84 regulator
85 requirements
86 results
87 risk
88 selection
89 seropositivity
90 signaling
91 single nucleotide polymorphisms
92 successful bone marrow transplantation
93 survival
94 total HLA mismatches
95 transplantation
96 unadjusted regression
97 unrelated bone marrow transplantation
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