SUPPLEMENTAL DATA
Bezzerri et al.
Table S1: Candidate genes
abbreviation
gene name
• Chemokines
CXCL2
GRO – beta
CXCL3
GRO – gamma
CC chemokine L1
CCL1
CCL2
MCP-1
CCL3
MIP-1alpha
CCL4
MIP-1beta
CCL7
MCP-3
CCL8
MCP-2
CCL11
eotaxin
CCL13
MCP-4
CCL23
MIP-3
CCL24
eotaxin-2
CCL26
eotaxin-3
CXCL10
IP-10
CXCL11
I-TAC
CXCL13
Angie
CXCL14
MIP-2gamma
• Receptors for chemokines
CXCR1
CXC 1 receptor (also IL-8 receptor)
CXCR2
CXC 2 receptor (also IL-8/GRO-a receptor)
CXCR7
CXC receptor 7
CCR1
C-C receptor 1
CCR3
C-C receptor 3
CCR6
C-C receptor 6
CCR7
C-C receptor 7
CCR9
C-C receptor 9
CCRL2
C-C receptor-like 2
FPRL1
FMLP-R-II or lipoxin A4-R
• Adhesion molecules
ICAM-1
Intercellular adhesion molecule 1
VCAM-1
Vascular adhesion protein 1
1
• Receptors involved in host – pathogen interactions
TLR2
Toll-like Receptor 2
TLR4
Toll-like Receptor 4
TLR5
Toll-like Receptor 5
• Cytokines
IL-1A
Interleukin 1 alpha
IL-1B
Interleukin 1 beta
IL-4
Interleukin 4
IL-6
Interleukin 6
IL-17C
Interleukin 17C
IL-18
Interleukin 18
TNFA
Tumor Necrosis Factor alpha
• Purinergic receptors
P2RY1
P2Y receptor 1
P2RY2
P2Y receptor 2
• Antimicrobial peptides
HNP4
Human Alpha defensin 4
HBD-1
Human Beta Defensin-1
CG
Catepsin G
AZU1
Azurocidin
•
System components generating reactive oxygen and nitrogen
species
p40Phox
SH3 and PX domain-containing protein 4
p67Phox
NADPH oxidase activator 2
NOX1
NADPH oxidase 1 variant NOH-1L
NOX2
NADPH oxidase 2
NOX3
NADPH oxidase catalytic subunit-like 3
NOX4
Kidney superoxide-producing NADPH oxidase
NOX5
NADPH oxidase 5
NOS1
Nitric oxide synthase 1
NOS2
Nitric oxide synthase 2
NOS3
Nitric oxide synthase 3
DUOX1
Flavoprotein NADPH oxidase 1
DUOX2
Flavoprotein NADPH oxidase 2
DUOXA1
Dual oxidase maturation factor 1
LPO
Lactoperoxydase
Transmembrane signaling in pro-inflammatory pathways:
PI3K (PI3-K catalytic/regulatory subunits and AKT)
PIK3R5
Phosphoinositide 3-kinase p101 class Ib regulatory
subunit
PIK3CA
Phosphoinositide 3-kinase p110 alpha, class Ia catalytic
subunit
PIK3CB
Phosphoinositide 3-kinase p110 beta, class Ia catalytic
2
PIK3CD
PIK3R1
PI3K p85
alpha
PI3K p85 beta
PI3Kgamma
AKT1
AKT2
AKT3
subunit
Phosphoinositide 3-kinase p110 delta, class Ia catalytic
subunit
Phosphoinositide 3-Kinase p50 alpha regulatory subunit
Phosphoinositide 3-Kinase p85 alpha regulatory subunit
Phosphoinositide 3-Kinase p85 beta catalytic subunit
Phosphoinositide 3-kinase gamma catalytic subunit
RAC-alpha serine/threonine-protein kinase
RAC-beta serine/threonine-protein kinase
RAC-gamma serine/threonine-protein kinase
•
Transmembrane signaling in pro-inflammatory pathways:
MAP kinases
MAPK14
p38 alpha
MAPK11
p38 beta
MAPK13
p38 delta
MAPK8
Jnk1
MAPK9
Jnk2
MAPK10
Jnk3
MAPK1
ERK2
•
Transmembrane signaling in pro-inflammatory pathways:
Cytoplasmatic Tyrosin Kinases
SRC
tyrosine-protein kinase SRC-1
FYN
tyrosine-protein kinase Fyn
YES
proto-oncogene tyrosine-protein kinase YES
LYN
tyrosine-protein kinase Lyn
HCK
tyrosine-protein kinase HCK
FGR
proto-oncogene tyrosine-protein kinase FGR
LCK
tyrosine-protein kinase Lck
ABL
tyrosine-protein kinase ABL1
BMX
epithelial and endothelial tyrosine kinase
TEC
tyrosine-protein kinase Tec
ZAP-70
zeta-chain associated protein kinase, 70kD
FAK1
protein-tyrosine kinase 2
FAK2
protein tyrosine kinase 2 beta
CSK
tyrosine-protein kinase CSK
•
Transmembrane signaling in pro-inflammatory pathways:
nuclear transcription factor NF-kB
TRAF1
TNF receptor-associated factor 1
TRAF2
TNF receptor-associated factor 2
TRAF3
TNF receptor-associated factor 3
TRAF4
TNF receptor-associated factor 4
TRAF5
TNF receptor-associated factor 5
TRAF6
TNF receptor-associated factor 6
IRAK1
Interleukin-1 Receptor Associated Kinase 1
3
IRAK2
IRAK4
NFKBIA
NFKBIB
NFKBIE
CHUK
IKBKB
Interleukin-1 Receptor Associated Kinase 2
Interleukin-1 Receptor Associated Kinase 4
Nuclear Factor of kappa light polypeptide gene enhancer
in B cell - inhibitor alpha
Nuclear Factor of kappa light polypeptide gene enhancer
in B cell - inhibitor beta
Nuclear Factor of kappa light polypeptide gene enhancer
in B cell - inhibitor epsilon
Conserved helix-loop-helix ubiquitous kinase
Inhibitor of k light polypeptide gene enhancer in B cell
kinase beta
•
Transmembrane signaling in pro-inflammatory pathways:
Small GTPases with their molecular targets
HRAS
V-Ha-RAS (Harvey rat sarcoma viral oncogene homolog)
NRAS
Neuroblastoma RAS viral (V-RAS) ncogène homolog
RHOA
RAS Homolog gene family member A
RHOC
RAS Homolog gene family member C
RHOG
RAS Homolog gene family member G
RAC1
RAS-related C3 botulinum toxin substrate 1
RAC2
RAS-related C3 botulinum toxin substrate 2
CDC42
Cell division cycle 42
ROCK1
Rho-Associated coiled-call containing protein K1
ROCK2
Rho-Associated coiled-call containing protein K2
PAK1
P21 protein-activated kinase 1
PAK2
P21 protein-activated kinase 2
•
Transmembrane signaling in pro-inflammatory pathways:
Phospholipases
PLA2G2A
Phospholipase A2, group IIA
PLA2G2D
Phospholipase A2, group IId
PLA2G2E
Phospholipase A2, group IIe
PLA2G2F
Phospholipase A2, group IIf
PLA2G3
Phospholipase A2, group III
PLA2G4A
Phospholipase A2, group IVa
PLA2G4B
Phospholipase A2, group IVB
PLA2G4C
Phospholipase A2, group IVC
PLCB1
Phospholipase C beta1
PLCB2
Phospholipase C beta2
PLCB3
Phospholipase C beta3
PLCB4
Phospholipase C beta4
PLCD1
Phospholipase C delta1
PLCD3
Phospholipase C delta3
PLCD4
Phospholipase C delta4
PLCE
Phospholipase C epsilon
PLCG1
Phospholipase C gamma1
PLCG2
Phospholipase C gamma2
4
Table S2
Single Nucleotide Polymorphisms (SNPs) selected
Chr
1
Gene_symbol (Gene_ID)
AKT3 (10000)
CDC42 (998)
FGR (2268)
LCK (3932)
NCF2 (4688) / p67 Phox
NRAS (4893)
PIK3CD (5293)
PLA2G2A (5320)
PLA2G2D (26279)
PLA2G2E (30814)
PLA2G2F (64600)
PLA2G4A (5321)
RHOC (389)
TLR5 (7100)
SNP_Name
rs4518884
rs1538773
rs9428576
rs1121276
rs2268177
rs2231878
rs35334091
rs11576032
rs11567841
rs695161
rs35012521
rs13306575
rs17849502
rs35937854
rs13306581
rs11578964
rs10911363
rs789185
rs969273
rs14804
rs28730673
rs4240910
rs1135427
rs4240896
rs9430220
rs6540991
rs34568801
rs1804275
rs584367
rs877064
rs11582551
rs12720588
rs2307198
rs2999156
rs12144044
rs7512943
rs5744176
rs5744175
rs5744171
rs5744168
rs4140966
rs5744167
Location
intron
intron
flanking_3UTR
intron
intron
coding
coding
coding
coding
intron
coding
coding
coding
coding
coding
intron
intron
intron
intron
3UTR
coding
intron
3UTR
intron
intron
intron
coding
coding
coding
intron
intron
coding
coding
intron
intron
coding
coding
coding
coding
coding
coding
coding
5
TRAF5 (7188)
VCAM1 (7412)
2
CXCR7 (57007)
IL1A (3552)
IL1B (3553)
IL8RA (3577) / CXCR1
IL8RB (3579) / CXCR2
PLCD4 (84812)
ROCK2 (9475)
3
ZAP70 (7535)
CCR1 (1230)
3
CCR3 (1232)
3
CCR9 (10803)
rs5744166
rs764535
rs3946808
rs2271458
rs4951523
rs10494936
rs6672742
rs34228330
rs34708918
rs3783611
rs3783612
rs34199378
rs3783615
rs3917012
rs3176877
rs3176861
rs3181088
rs3176860
rs10183022
rs7585641
rs1045879
rs3783531
rs3783550
rs1143634
rs1143643
rs16858811
rs10201766
rs1126579
rs658378
rs34945852
rs35768389
rs9808232
rs13397757
rs10194620
rs6730673
rs4669702
rs4477886
rs3192177
rs6781048
rs41413045
rs41393844
rs41276533
rs9854776
rs6441948
rs9853223
rs3091309
rs12721497
rs9862611
coding
coding
coding
coding
intron
intron
intron
coding
coding
coding
coding
coding
coding
intron
intron
intron
intron
intron
intron
intron
coding
coding
intron
coding
intron
coding
coding
3UTR
intron
coding
coding
coding
intron
intron
intron
intron
intron
coding
coding
coding
coding
coding
intron
intron
intron
intron
coding
intron
6
3
3
CCRL2 (9034)
CXCR6 (10663)
3
IRAK2 (3656)
3
3
P2RY1 (5028)
PAK2 (5062)
3
PIK3CA (5290)
3
PIK3CB (5291)
3
PLCD1 (5333)
rs7614342
rs6441977
rs2234355
rs2234356
rs2234357
rs2234358
rs936939
rs3774634
rs35060588
rs11465910
rs11465930
rs2302859
rs6442159
rs155266
rs1177614
rs11465897
rs11706450
rs11465853
rs263413
rs2619508
rs1642736
rs1169670
rs3844279
rs708030
rs776514
rs1144911
rs701265
rs9877495
rs2084382
rs7626440
rs6583177
rs11923075
rs9222
rs7649045
rs4916555
rs6583176
rs2686600
rs17849072
rs41273621
rs2699905
rs2677760
rs1607237
rs6443624
rs558905
rs10513055
rs9837637
rs933135
rs2268749
intron
coding
coding
coding
coding
3UTR
intron
intron
coding
coding
coding
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
coding
intron
intron
intron
intron
intron
3UTR
intron
intron
intron
intron
coding
coding
intron
intron
intron
intron
intron
intron
coding
coding
intron
7
3
4
RHOA (387)
CXCL10 (3627)
CXCL11 (6373)
CXCL13 (10563)
CXCL2 (2920)
CXCL3 (2921)
MAPK10 (5602) / JNK3
SLAIN2 (57606)
SPP1 (6696)
TEC (7006)
TLR2 (7097)
rs9857730
rs11706370
rs1126858
rs4859586
rs4859596
rs7436646
rs355674
rs355686
rs355667
rs920666
rs355689
rs1500500
rs9131
rs6832638
rs370655
rs2904100
rs17451306
rs17417758
rs4487330
rs10516763
rs9884282
rs4693141
rs7665868
rs10009993
rs12507758
rs6815306
rs1460769
rs1436529
rs17418221
rs1460767
rs10938526
rs9138
rs35374286
rs2089511
rs17574847
rs17470919
rs2704425
rs7687704
rs17574371
rs4695356
rs2704421
rs12643804
rs11725773
rs2664019
rs2704423
rs5743699
rs5743702
rs5743703
coding
intron
coding
intron
coding
3UTR
intron
intron
intron
intron
intron
intron
3UTR
coding
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
flanking_5UTR
3UTR
coding
intron
flanking_5UTR
intron
intron
intron
coding
intron
intron
flanking_5UTR
intron
intron
intron
coding
coding
coding
8
5
CXCL14 (9547)
IL4 (3565)
MAPK9 (5601) / JNK2
PIK3R1 (5295)
6
CCR6 (1235)
FYN (2534)
rs5743704
rs3804099
rs11938228
rs1898830
rs1016666
rs2237062
rs1148360
rs4986964
rs2227282
rs35693958
rs35421153
rs17627536
rs4481314
rs3111515
rs6868333
rs6863088
rs4147385
rs3730089
rs6863431
rs1819987
rs251409
rs34306
rs6881033
rs251408
rs1445760
rs251406
rs4122269
rs12652661
rs1823023
rs173702
rs17860852
rs1571878
rs3093012
rs3093009
rs2071171
rs1855025
rs3093010
rs28763975
rs6568704
rs6933144
rs804188
rs11963612
rs13192832
rs12910
rs804192
rs927010
rs13218316
rs1621289
coding
coding
intron
intron
intron
intron
intron
coding
intron
coding
coding
intron
intron
intron
intron
intron
intron
coding
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
coding
intron
intron
intron
coding
intron
intron
coding
intron
intron
intron
intron
intron
UTR
intron
intron
intron
intron
9
MAPK13 (5603) / p38delta
MAPK14 (1432) / p38alpha
NFKBIE (4794)
NOX3 (50508)
TNF (7124)
7
CCL24 (6369)
CCL26 (10344)
IL6 (3569)
NOS3 (4846)
PIK3CG (5294)
rs706862
rs1327200
rs7768046
rs706895
rs2071864
rs851010
rs3804454
rs851006
rs35500460
rs730775
rs3749930
rs13207865
rs231960
rs231955
rs231961
rs6935359
rs6557421
rs12196156
rs231944
rs231947
rs1016259
rs2235675
rs9371890
rs9478652
rs231948
rs438239
rs2235674
rs35131721
rs11574936
rs2302004
rs11465333
rs41341147
rs41463245
rs2302009
rs11544633
rs2069840
rs3918166
rs1799983
rs41508746
rs3918201
rs1800783
rs3918188
rs17847825
rs28763989
rs28763991
rs4730205
rs4460309
rs12536620
intron
intron
flanking_5UTR
intron
intron
intron
intron
intron
coding
intron
coding
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
coding
coding
intron
coding
coding
coding
3UTR
coding
intron
coding
coding
coding
coding
intron
intron
coding
coding
coding
intron
intron
intron
10
RAC1 (5879)
8
DEFA4 (1669)
DEFB1 (1672)
IKBKB (3551)
LYN (4067)
PTK2 (5747) / FAK1
PTK2B (2185) / FAK2
9
ABL1 (25)
rs3729790
rs702484
rs2239668
rs2977779
rs6991366
rs2272736
rs17875749
rs34309584
rs10958713
rs3747811
rs5029748
rs907424
rs2668015
rs16922502
rs2292419
rs4436100
rs2719245
rs1027990
rs7834615
rs10282821
rs7828258
rs2668021
rs7829816
rs333616
rs13249338
rs7005312
rs6983130
rs4563941
rs12156014
rs10109684
rs6993266
rs7839119
rs13270490
rs13257119
rs7827949
rs41276291
rs35174236
rs751019
rs41276293
rs7000615
rs11995441
rs1019832
rs17057051
rs2322599
rs10086852
rs10097861
rs34549764
rs2229071
intron
intron
intron
intron
coding
coding
coding
coding
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
coding
coding
coding
coding
intron
intron
intron
intron
intron
intron
intron
coding
coding
11
TLR4 (7099)
TRAF1 (7185)
TRAF2 (7186)
10
CHUK (1147) / IKKalpha
MAPK8 (5599) / JNK1
PLCE1 (51196)
rs10901275
rs2791738
rs2855172
rs12005009
rs10901285
rs11788639
rs2791743
rs2855171
rs5030718
rs5030719
rs34953464
rs5030720
rs5030722
rs5030723
rs5030724
rs5030728
rs1927911
rs36084135
rs34119250
rs7021049
rs10870140
rs2784081
rs4880073
rs10781522
rs2230804
rs36065428
rs11597086
rs7086275
rs12358297
rs10508901
rs17508082
rs17417407
rs11596200
rs12768416
rs11187829
rs2274224
rs41291138
rs3765524
rs2274223
rs7917353
rs10882416
rs7919320
rs2689698
rs11187820
rs9663362
rs1223635
rs11187792
rs11187851
intron
intron
intron
intron
intron
intron
intron
intron
coding
coding
coding
coding
coding
coding
coding
intron
intron
coding
coding
intron
intron
intron
intron
intron
coding
coding
intron
intron
intron
intron
coding
coding
coding
coding
coding
coding
coding
coding
coding
intron
intron
intron
intron
intron
intron
intron
intron
intron
12
11
IL18 (3606)
NOX4 (50507)
P2RY2 (5029)
PAK1 (5058)
PLCB3 (5331)
RHOG (391)
TRAF6 (7189)
12
IRAK4 (51135)
12
KRAS (3845)
12
NOS1 (4842)
rs2689694
rs17415514
rs17109869
rs2797992
rs12769135
rs2797986
rs17416616
rs4918082
rs1858608
rs2077218
rs5744258
rs549908
rs317139
rs10765208
rs317155
rs3793973
rs12799930
rs497279
rs3741156
rs1783596
rs35345144
rs2250647
rs478134
rs35169799
rs3815362
rs2244625
rs1451722
rs1349542
rs10835184
rs10835182
rs34320471
rs5030419
rs4251469
rs4251583
rs4251545
rs4251513
rs4368021
rs12226937
rs12579073
rs10842514
rs9658482
rs9658445
rs41356652
rs9658356
rs4519169
rs9658279
rs2291908
rs7977109
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
coding
coding
intron
intron
intron
intron
intron
coding
coding
coding
intron
intron
coding
intron
coding
intron
intron
intron
intron
coding
intron
coding
coding
coding
intron
intron
intron
intron
intron
coding
coding
coding
coding
coding
coding
intron
intron
13
14
AKT1 (207)
CTSG (1511) / catepsin G
NFKBIA (4792)
TRAF3 (7187)
15
CSK (1445)
DUOX1 (53905)
DUOX2 (50506)
DUOXA1 (90527)
NOX5 (79400)
PLA2G4B (8681)
PLCB2 (5330)
16
IL17C (27189)
PLCG2 (5336)
rs3782218
rs816361
rs693534
rs3782221
rs1123425
rs12578547
rs547954
rs6490121
rs545654
rs1130214
rs11623400
rs696
rs7154305
rs12878111
rs10137035
rs34866753
rs34616395
rs35556162
rs2301249
rs1378942
rs1648305
rs16939752
rs2458236
rs269866
rs269868
rs1648281
rs34406284
rs12907196
rs2277553
rs2277552
rs7167318
rs7168025
rs12899318
rs371352
rs4777102
rs7174710
rs2290552
rs936212
rs9972332
rs8025153
rs2305650
rs936213
rs1123487
rs1869901
rs2254073
rs9936371
rs17537869
rs3935625
intron
intron
intron
intron
intron
intron
intron
intron
intron
5UTR
intron
3UTR
intron
intron
intron
coding
coding
coding
intron
intron
intron
coding
coding
intron
coding
UTR
coding
coding
coding
coding
coding
coding
intron
intron
intron
coding
coding
coding
coding
coding
intron
intron
intron
intron
intron
coding
coding
coding
14
17
CCL1 (6346)
CCL11 (6356)
CCL13 (6357)
CCL2 (6347)
CCL23 (6368)
CCL3 (6348)
CCL4 (6351)
CCL7 (6354)
CCL8 (6355)
CCR7 (1236)
LPO (4025)
NOS2A (4843)
rs8063604
rs12716922
rs8054878
rs4405545
rs7189843
rs8043619
rs4077853
rs1143686
rs9928191
rs12444459
rs4580153
rs4889384
rs4243225
rs3936112
rs3934956
rs9938212
rs9932716
rs4580154
rs13333420
rs8055576
rs3922849
rs6564928
rs12444401
rs4888182
rs2282691
rs34262946
rs1860184
rs3136677
rs34566308
rs159313
rs4586
rs1003645
rs1130371
rs1719152
rs1634517
rs3091321
rs41362546
rs1133763
rs34202026
rs2023906
rs7219860
rs11868650
rs2301870
rs2314808
rs28944173
rs2297518
rs944725
rs9906835
intron
intron
intron
intron
intron
intron
intron
coding
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
coding
intron
coding
coding
intron
coding
coding
coding
coding
intron
intron
coding
coding
coding
intron
intron
intron
coding
coding
coding
coding
intron
intron
15
PIK3R5 (23533) / p101
PLCD3 (113026)
TRAF4 (9618)
18
ROCK1 (6093)
YES1 (7525)
19
AKT2 (208)
AZU1 (566)
FPR1 (2357) / FMLP
ICAM1 (3383)
NFKBIB (4793)
PLA2G4C (8605)
rs4795067
rs8072199
rs3729508
rs419849
rs181531
rs12945251
rs394811
rs16957702
rs734921
rs34721135
rs3744760
rs1052169
rs713101
rs35932778
rs35100992
rs2070265
rs2663698
rs1045142
rs35881519
rs2292296
rs2271255
rs8085654
rs288980
rs2663695
rs1481280
rs35126906
rs34580680
rs1060922
rs3897601
rs8093865
rs35817154
rs12460555
rs12460890
rs5030878
rs5491
rs422429
rs1799969
rs34369517
rs5495
rs5497
rs5030400
rs281432
rs8108039
rs3136640
rs35229843
rs11564638
rs11564620
rs11564541
intron
intron
intron
intron
intron
intron
coding
coding
coding
coding
intron
3UTR
coding
coding
coding
coding
coding
coding
coding
coding
coding
intron
intron
intron
intron
coding
coding
3UTR
flanking_5UTR
flanking_5UTR
coding
intron
coding
coding
coding
coding
coding
coding
coding
coding
coding
intron
intron
intron
coding
coding
coding
coding
16
20
HCK (3055)
PLCB1 (23236)
rs156631
rs11564538
rs6089165
rs6089166
rs17093828
rs13037181
rs13041270
rs13042803
rs6086575
rs28390202
rs6086672
rs6056072
rs6077418
rs2745784
rs3848832
rs6140583
rs6056094
rs6118283
rs2294259
rs708926
rs6055628
rs4399790
rs2745769
rs718986
rs6140770
rs6055697
rs4813865
rs2179137
rs12481262
rs6077404
rs6039215
rs1238231
rs2876140
rs6086506
rs708910
rs6039208
rs6108205
rs6133613
rs761042
rs2235947
rs6108195
rs1232779
rs11087811
rs6039209
rs2719795
rs2745787
rs2076685
rs2663004
coding
coding
coding
coding
coding
coding
coding
coding
coding
coding
intron
intron
intron
intron
intron
intron
intron
intron
intron
flanking_3UTR
intron
intron
intron
intron
intron
intron
flanking_5UTR
intron
intron
intron
intron
flanking_3UTR
intron
flanking_5UTR
3UTR
flanking_5UTR
intron
intron
intron
intron
intron
flanking_3UTR
flanking_5UTR
intron
flanking_3UTR
intron
intron
intron
17
PLCB4 (5332)
rs6077428
rs6039051
rs1028370
rs17446441
rs6140561
rs6055652
rs17446308
rs6516403
rs2207306
rs6086518
rs13037679
rs6055991
rs6039109
rs1509116
rs6055928
rs6140546
rs1474937
rs6140549
rs6056037
rs6118083
rs13040543
rs6077332
rs6086403
rs6055562
rs4496390
rs2719775
rs4419296
rs1509117
rs2327044
rs4813853
rs2179138
rs1232784
rs6077510
rs6118603
rs8183759
rs6108299
rs16995736
rs6056596
rs6039432
rs984010
rs2072954
rs6118505
rs6108280
rs926395
rs725941
rs2208295
rs2179321
rs5011374
intron
intron
intron
intron
intron
intron
intron
intron
intron
flanking_5UTR
intron
intron
intron
intron
flanking_5UTR
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
flanking_5UTR
intron
flanking_5UTR
intron
intron
intron
coding
coding
coding
coding
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
intron
18
PLCG1 (5335)
SRC (6714)
22
MAPK1 (5594) / ERK2
MAPK11 (5600) / p38beta
NCF4 (4689) / p40
PLA2G3 (50487)
RAC2 (5880)
rs3819579
rs6056522
rs6056437
rs4369940
rs6118591
rs6056519
rs2229348
rs2228246
rs7266677
rs6065316
rs34203315
rs753381
rs2235361
rs2076146
rs3795131
rs6093446
rs6018260
rs34881773
rs6017944
rs1547836
rs6018027
rs12106024
rs1063311
rs9610487
rs8136867
rs2298432
rs33932986
rs2076139
rs2066776
rs35396905
rs34422484
rs2272857
rs742184
rs13057803
rs9610595
rs35355915
rs3827352
rs738148
rs760519
rs2284027
rs746713
rs4821544
rs2232183
rs2074735
rs2074734
rs2232176
rs8135343
rs13058338
intron
intron
intron
intron
intron
intron
coding
coding
coding
coding
coding
coding
coding
intron
intron
intron
coding
coding
intron
intron
intron
intron
3UTR
intron
intron
intron
coding
coding
coding
coding
coding
coding
intron
coding
coding
coding
intron
intron
intron
intron
intron
intron
coding
coding
coding
coding
intron
intron
19
X
BMX (660)
IRAK1 (3654)
NOX1 (27035)
rs739041
rs6572
rs35353387
rs41300892
rs12860727
rs34688635
rs35242502
intron
3UTR
coding
coding
coding
coding
coding
20
Table S3
Ranking of statistical significance of association of the SNPs analyzed
Rank
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
Gene
PLCB3
NOS2
PAK2
CXCL13
CXCR6
PLCB1
LYN
LYN
NOS2
PLA2G4C
PLCB1
CXCR6
PIK3R1
NOX3
YES1
FYN
ABL1
MAPK8
ABL1
P2RY2
ABL1
PLCB1
PLCB4
PLCE1
MAPK11
IL17C
SNP
RS35169799
RS3729508
RS6583177
RS355689
RS2234355
RS6086479
RS7828258
RS13249338
RS8072199
RS11564538
RS6086403
RS3774634
RS6863431
RS1016259
RS3897601
RS13218316
RS2855171
RS12358297
RS2229071
RS1783596
RS2791738
RS2876140
RS5011374
RS2274223
RS2076139
RS2254073
P_Value
0.00465
0.01028
0.0169
0.01776
0.01938
0.01962
0.02039
0.02146
0.02172
0.02371
0.02664
0.02705
0.02926
0.03004
0.0305
0.03379
0.03413
0.03654
0.04079
0.04147
0.0416
0.04523
0.04545
0.04729
0.04762
0.04839
Table reports the ranking of significance of association with
mild or severe phenotype for P values < 0.05, as calculated by permutation test
21
Table S4
Primers for quantification of gene transcripts
Primer
IL 8-F
Sequence (5′–3′)
GACCACACTGCGCCAACA
GCTCTCTTCCATCAGAAAGTTACATAAT
IL 8-R
TT
PLCb1-F CAGCTCTTCTGGAATGCAGGT
PLCb1-R TTTATTTGCATAGCCAGGTCC
PLCb2-F ATGTTCTGGAATGCTGGA
PLCb2-R TGCTGCATGGGCAAGTC
PLCb3-F TCTTCTGGAACGTAGGG
PLCb3-R AGCTGCATCGCCACATC
PLCb4-F CCTCAGATTTTCTGGAACGCTGGC
PLCb4-R TTCAATTGCATCGCTAAATC
PLCd1-F GGACGGAGGCTGGGCCTACA
PLCd1-R GGAGCTGGCTGCCCTTCAGCAG
PLCd3-F ACCCTGCCAGGTCAGCTCCC
PLCd3-R AGCTGTTCCCTGCCTCCCGA
PLCd4-F GGGGGACCAGCTTTGCGGC
PLCd4-R CCCCGCTTCAGGGCCCGTAT
PLCg1-F GACCTTCATCAAGAGCGCCA
PLCg1-R CCCCTCGCCACCAGCCTCCC
PLCg2-F GAGCTTCTGCCGTGGTGCCC
PLCg2-R CTCCTTTCCACCAGCCCCCG
PLCe1-F AGGCCAGTGTCCTCCCCTGTG
PLCe1-R AGCCCATCCAGTGCTTGGAGC
GAPDH-F GTGGAGTCCACTGGCGTCTT
GAPDHGCAAATGAGCCCAGCCTTC
R
G6PD-F
GCCAAGAAGAAGATCTACCCCA
G6PD-R
AAGGCCATCCCGGAACAG
RPII-F
TCGAGCAGATCAGCAAGGTG
RPII-R
TCTTGTTGTCTGTCTGTGGCAA
eEF1g-F
AAACTGTGTGAGAAGATGGCCC
eEF1g-R GGGTCTCTGCAAACTTTTTAGCA
CK 15-F GGCTGGCTGCGGACG
CK 15-R GCAGGGCCAGCTCATTCTC
Accession
Number
AF385628.2
mM
15
Calibrator
gene
GAPDH
15
NM_015192
2.5
15
NM_004573
15
15
NM_000932
15
2.5
NM_000933
15
2.5
NM_001130964 15
15
NM_133373
45
2.5
NM_032726
2.5
15
NM_002660
45
45
NM_002661
2.5
2.5
NM_016341
2.5
15
J04038
2.5
GAPDH
GAPDH
eEF1g
eEF1g
G6PD
G6PD
RPII
G6PD
CK-15
G6PD
15
NM_000402.2
NM_000937.2
NM_001404.3
NM_002275
15
2.5
2.5
2.5
15
2.5
15
15
22
Supplementary Table 5 - Genotype of the SNPs of the PLC family in the top rank of
Major/minor aminoacid
GENE
SNP
alleles
change
PLCB3 RS35169799
C/T
S845L
PLCB1 RS6086479
C/T
no change
PLCB1 RS6086403
A/C
no change
PLCB1 RS2876140
A/G
no change
PLCB4 RS5011374
A/C
no change
PLCE1 RS2274223
A/G
H1619R
association with severe or mild CF lung progression
IB3-1
CuFi-1
Chromosome genotype genotype
11
C/C
C/C
20 (intronic)
C/T
C/C
20 (intronic)
A/C
A/C
20 (intronic)
A/G
A/G
20 (intronic)
A/C
A/A
10
A/A
A/A
23
GENE
PLCB3
PLCB1
PLCB1
PLCB1
PLCB4
PLCE1
Forward
GATACCACTACGTCTGCC
CTTTCTGTGTATGAGGGAGGAA
AGCCTCTGCTGGTGTATGCT
GTCCGGTTGAATTTTGGGTA
AAACCCTCTTGGAGAGAGCTG
CAGAATGTGTGCCCCAGTAAT
Reverse
CCTGGTGGTCGTCAGGAATG
CCCATAAATGCACCCCATAA
CCAGTAGTGCCCAGGAGAAA
TCCAATCAGTCTTGTCATTCAA
ACAACGAGGCTAAGGAGCAC
GCTTTCAGTGGAATGATTCTC
Supplementary Table 6 – Sequencing primers for PLC family SNPs
24
Figure S1
Expression and silencing of phospholipase C beta (PLCB) isoforms in IB3-1 cells
Expression of PLC mRNA of the PLC isoforms beta 1 to beta 4 was quantified by qRT-PCR
relative to the levels of expression of the housekeeping gene cytokeratin (CK)-15 after transfection
of siRNA PLCB3 or scrambled oligonucleotides
26
Figure S2
Relative transcript expression levels of PLC isoforms
in CF bronchial epithelial IB3-1 and CuFi-1 cell lines
Expression of PLC mRNA of the PLC isoforms beta, gamma, delta and epsilon was quantified by
qRT-PCR relative to the levels of expression of the housekeeping gene cytokeratin (CK)-15.
27