According the inflammatory nature of PVR,
2,27 the following 30 candidate genes were investigated in the discovery stage: connective tissue growth factor (
CTGF), epidermal growth factor (
EGF), fibroblast growth factor (
FGF), hepatocyte growth factor (
HGF), insulin-like growth factor 1 (
IGF-1), interferon gamma (
IFNG), insulin-like growth factor 2 (
IGF-2), insulin-like growth factor I receptor (
IGF1R), interleukin 1 alpha (
IL1A), interleukin 1 beta (
IL1B), interleukin 1 receptor antagonist (
IL1RN), interleukin 6 (
IL6), interleukin 8 (
IL8), interleukin 10 (
IL10), monocyte chemotactic protein 1 (
MCP1), macrophage migration inhibitory factor (
MIF), matrix metalloproteinase (
MMP)-
2, matrix metalloproteinase 7 (
MMP7), nuclear factor kappa-b subunit 1 (
NFKB1), nuclear factor of kappa light chain gene enhacer in B cells inhibitor alpha (
NFKBIA), nuclear factor of kappa light chain gene enhacer in B cells inhibitor beta (
NFKBIB), platelet-derived growth factor (
PDGF), platelet-derived growth factor receptor alpha (
PDGFRα),
PI3K,
SMAD3,
SMAD7, transforming growth fator beta 1 (
TGF-β1), transforming growth fatcor beta 2 (
TGF-β2), tumor necrosis factor alpha (
TNF-α), and tumor necrosis factor receptor 2 (
TNFR2). Common tag SNPs with correlation coefficients greater than or equal to 0.85 and a minor allelic frequency greater than or equal to 10% were studied to explain as much as possible the known genetic variation for each gene. The Tagger method implemented in the Haploview program (provided in the public domain by Broad Institute;
http://www.broad.mit.edu/mpg/haploview/) was used for this purpose.
28 According to the linkage disequilibrium observed in the
TNF-α region, the following four genes were necessary to be investigated in the
TNF locus: lymphotoxin alpha (
LTα),
TNF-α, leucocyte specific transcript 1 (
LST1), and the activating natural killer receptor p30 (
NCR3). Genic and extragenic regions 10 kb upstream and downstream were considered for each gene. Functional SNPs or ones previously described in association with other inflammatory diseases were added for analysis.
29–33 In the replication stage same SNPs previously studied in
PIK3CG,
SMAD7,
TNF locus, and
TNFR2 (30 SNPs) were investigated.