Genes and Immunity (2006) 7, 269276

& 2006 Nature Publishing Group All rights reserved 1466-4879/06 $30.00
www.nature.com/gene

REVIEW

Cytokine gene polymorphism in human disease: on-line

databases, Supplement 3
MV Hollegaard1,2,3 and JL Bidwell4
NANEA at Department of Epidemiology, Institute of Public Health, University of Aarhus, Aarhus, Denmark; 2Department of Clinical
Biochemistry Statens Serum Institut, Copenhagen, Denmark; 3Department of Biochemistry and Molecular Biology, University of
Southern Denmark, Odense, Denmark and 4Department of Pathology and Microbiology, University of Bristol, Homeopathic Hospital
Site, Cotham, Bristol, UK
1

Within the past few years, the focus on cytokine single nucleotide polymorphism (SNP) function and association with human
diseases has increased considerably. This third supplement to the Cytokine Gene Polymorphism in Human Disease: On-line
database describes the positive associations of cytokine SNPs in human diseases described in articles published from 2002 up
to 2005. A file containing a list of all SNPs investigated in this period of time and their association with human disease or
expression pattern can be downloaded from the internet address http://www.nanea.dk/cytokinesnps/. The web pages also
contain other features and downloads that could be useful when planning cytokine SNP association studies.
Genes and Immunity (2006) 7, 269276. doi:10.1038/sj.gene.6364301; published online 27 April 2006
Keywords: cytokine; SNP; polymorphism; variation; disease; expression

Introduction
The Cytokine Gene Polymorphism in Human Disease:
on-line database was first published in Genes and
Immunity in 1999.1 The first update, supplement 1, came
in 20012 and supplement 2 in 2002.3 Supplement 3
updates the database with articles from 2002 to early
2005. As the number of articles investigating cytokine
single nucleotide polymorphism (SNP)disease associations has increased substantially in the past few years
and as this supplement covers more than 1 year, we have
chosen only to show the SNPs that have an association
with a specific disease in Table 1. A full version of
supplement 3 is available for download from the on-line
database at the new permanent web address www.
nanea.dk/cytokinesnps/. This version includes links to
PubMed as well as the SNPs that was not found to be
associated with a disease. A few changes have been
made in this supplement compared to earlier issues, the
most prominent one being that the data are presented in
a Microsoft Excel spreadsheet, allowing the reader to
search and sort the SNPs, authors and diseases. With
regard to naming of the SNPs, we have chosen to use the
OMIM gene names (http://www.ncbi.nlm.nih.gov) and
furthermore, we have grouped those SNPs that have
numerous names under one name. For example, TNFA

308 G4A is also known as TNF NcoI or TNF1/2: in this
Correspondence: MV Hollegaard, Department of Clinical Biochemistry, Statens Serum Institut, Artillerivej 5, Copenhagen 2300,
Denmark.
E-mail: mvh@ssi.dk
Received 2 March 2006; accepted 9 March 2006; published online 27
April 2006

new supplement, it is named TNF
307 G4A (
308,

TNF1/2, NcoI). We would like to encourage authors
of SNP studies to supply the readers with an SNP rs
number and OMIM gene names.
Not all genes in the supplement are cytokines, but
those that are not, are included because they were
investigated in the same study as the cytokine genes. We
are aware that some articles could be absent in this and
previous supplement updates as we have chosen to use
PubMed as our primary article source and have stringent
search criteria. Furthermore, we have excluded manuscripts if they were difficult to obtain, not written in
English or it was not clear which SNPs were investigated. To correct, add or change interpreted data in
supplement 3, we encourage authors to contact the
corresponding author. Besides the association studies,
the new website also contains an Excel spreadsheet
containing the in vivo/vitro studies.
The web pages have been redesigned to amalgamate
all data from the previously published initial review, two
previous supplements and the present supplement. A
new feature is the Links Navigator page, which provides
links to: the CHIP Bioinformatics SNP per entries for
each gene (http://snpper.chip.org/);4 the appropriate
gene in the UCSC Genome Bioinformatics site (http://
genome.cse.ucsc.edu/);5 the appropriate intra-site entries
on the polymorphism, expression and disease association pages (see navigation bar to the left of the main
window in Figure 1) and finally to annotated nucleotide
sequence alignments where available. In the Links
Navigator, genes have been grouped into five classes:
TNF superfamily ligands and receptors; interleukin
ligands/antagonists and interleukin receptors and
other cytokines/growth factors/receptors. The data

Cytokine gene polymorphism in human disease

MV Hollegaard and JL Bidwell

270

Table 1 In vivo disease-association studies

Disease

Yes

Acute appendicitis
Acute lung injury
Acute lymphoblastic leukemia
Acute rejection
Acute renal failure
Acute resistance exercise
Aggressive lymphoma
Aggressive periodontitis
AIDS
Alcoholism
Allergic asthma

IL6
174 C4G

PBEF
1001 T4G, PBEF
1543 C4T
IL10
1117 T4C, TNF
307 G4A
IL10
854 T4C, IL10 haplotypes, IL2 n repeat, TNF
307 G4A
IL10
1117 T4C, TNF
307 G4A
IL1A +4845 G4T, IL1B +3953 C4T, IL1B
3737, IL1B
511 C4T, IL1RN +2018 T4C
IL10
1117 T4C
IL1B +3953 C4T
IL4 IL10 haplotypes, 64 SNPs, IL10
627 C4A, IFNG
179 T4G
IL6
174 C4G
IL4R +148 A4G, IL4R +1902 G4T, IL13 +2044, IL1A +4845 G4T, IL1B
511 C4T, IL1RN 86 bp VNTR,
TGFB1 869 C4T, TGFB1 915 G4C, TNF
307 G4A
TNF
307 G4A
IFNG +874 A4T, IL10
1117 T4C, IL10
627 C4A, IL10
854 T4C, IL2
330 T4G, IL6
174 C4G,
TGFB1 869 C4T, TGFB1 915 G4C, TNF
307 G4A
IL1-L1+4734, IL1RN +2018 T4C, IL1RN 86 bp VNTR
IL13 +2044, IL13
1111 C4T, IL4
590 C4T, IL4R +148 A4G, IL4R +1682 T4C, IL4R +1902 G4T

Allergic contact dermatitis

Allograft function
Alopecia areata
Alopecia totalis alopecia
universalis
Alzheimer disease
Amyloid A amyloidosis
Angiotensin-converting enzyme
Ankylosing spondylitis
Asthma

Atherogenesis
Atherosclerosis
Atopic asthma
Atopic eczema
Atopic rhinitis
Atopy
Atrial fibrillation
Atrophic gastritis
Attention-deficit4hyperactivity
disorder
AV fistula patency
Basal cell carcinoma
Behcets disease
Be-hypersensitivity
Bipolar I disorder
Bladder cancer
Bladder tumors
Blood pressure
Body mass index
Bone marrow transplantation
Bone mineral density

Brain arteriovenous
malformation
Breast cancer
Bronchial asthma
Bronchopulmonary dysplasia
C. pneumoniae infection
Calcific aortic stenosis
Cardiac surgery
Cardiovascular disease
Carotid atherosclerosis
Carotid intimal-medial wall
thickness

Genes and Immunity

IL10
1117 T4C, IL6
174 C4G, IL10
1117 T4C, IL10
627 C4A, IL10
854 T4C, IL1A
889 C4T,
IL1B +3953 C4T, IL1B
511 C4T, IL1RN 86 bp VNTR, IL6
174 C4G, IL6 30 UTR VNTR, TNF
1032
T4C, TNF
857 C4T, TNF
863 C4A
IL1B
511 C4T
PAI1
675 4G45G
IL1RN 30735 T4C, IL1RN 31017 G4C, IL1RN 86 bp VNTR
IL10
1117 T4C, IL10
627 C4A, IL10
854 T4C, IL12B +4237 G4A, IL12B +6402 A4C, IL12B
promoter, IL15 +10504 A4G, IL15 +13687 C4A, IL15 +14035 A4T, IL15 +267 C4T, IL15 +367 G4A, IL18

137 G4C, IL1B
511 C4T, IL3 +79 T4C, IL4
33 C4T, IL4
590 C4T, IL4 int3 70 bp VNTR, IL4R
+1902 G4T, IL8
251 T4A, TLR4 +896 A4G, TNF
1032 T4C, TNF
307 G4A, TNF
857 C4T, TNF

863 C4A
TLR4 +896 A4G
IL6
174 C4G
CCL5
403 G4A, haplotypes TNF24DRB1*03 TNF24*B1*1104, IL4R +148 A4G, IL4R +1902 G4T,
IL4R
3223 C4T, TNF
307 G4A, IL12B
1188 A4C, IL13 +2044, IL13 +4257 G4A, IL13
1111 C4T,
IL4
590 C4T, IL4R +148 A4G, IL4R
3223 C4T
IL4R +1902 G4T
IL4R 1432 T4C
IL13 +2044, IL18
137 G4C, IL18
607 C4A, IL1A +4845 G4T, IL1RN 86 bp VNTR, IL4R +1902 G4T
IL6
174 C4G
IL1B
31 T4C
IL1RN 86 bp VNTR
TGFB1 869 C4T, TGFB1 915 G4C
MTHFR +677 C4T
TNF
1032 T4C, TNF
237 G4A, IL1A
889 C4T, IL1B +3953 C4T
TNF
307 G4A, TNF
857 C4T
TNF
307 G4A
IL4 int3 70 bp VNTR, TNF
307 G4A, VEGF
2578 C4A
TNF
307 G4A
IL1B
511 C4T, TNF
307 G4A
IL6
174 C4G, IL6 CA repeat, TNF
307 G4A
IL1A
889 C4T, IL1B
511 C4T, TGFB1 869 C4T, TGFB1TII 1167 C4T, TNF
1032 T4C, TNF
857
C4T, TNF
863 C4A, TNFRSF1B +676 G4T
CCR2 +190 G4A, IL10
627 C4A, IL1RN 86 bp VNTR, IL6
174 C4G, IL6
572 G4C, IL6
634 C4G,
IL6 CA repeat, LTA +252 A4G, OPG 209 G4A, OPG 245 T4G, OPG A163G, PLOD1 +84 G4A, PLOD1
1097 G4A, PLOD1 1406 T4C, PLOD1 1734 C4T, PLOD1 1832 A4C, PLOD1 1988 G4T, PLOD1 2324
T4C, PLOD1 2333 C4G, PLOD1 494 C4T , PLOD1 495 G4A, PLOD1 G-86A, PLOD1 T-17G, TNF
1032
T4C, TNF
307 G4A, TNF
857 C4T, TNF
863 C4A, TNFRSF1B +1663 G4A, TNFRSF1B +1668
T4G, TNFRSF1B +1690 T4C, TNFRSF1B +593 G4A, TNFRSF1B +598 T4G, TNFRSF1B +620 T4C,
TNFRSF1B +676 G4T, VDR 2 C4T
IL6
174 C4G
IL6
174 C4G
IL5
703 C4T
TNF
307 G4A
CD14
260 C4T
IL10
1117 T4C, IL10
627 C4A, IL10
854 T4C
TNF
307 G4A
IL10
1117 T4C, IL6
174 C4G, TGFB1 915 G4C
IL1RN 86 bp VNTR
IL6
174 C4G

Cytokine gene polymorphism in human disease

MV Hollegaard and JL Bidwell

271

Table 1 Continued
Disease

Yes

IL6
174 C4G

LTA +252 A4G, TNF
307 G4A
IL1A
889 C4T, IL1RN 86 bp VNTR, LTA +252 A4G, TNF
307 G4A
IL6
174 C4G
TNF
1032 T4C, TNF
237 G4A, TNF
307 G4A, TNF
857 C4T, TNF
863 C4A
IL10
1117 T4C
IFNA +551 T4G, IL1RN 86 bp VNTR, TNF
237 G4A, TNF
375 G4A, TNF
572 A4C, TNF
857
C4T, TNF
863 C4A
Cervical intra-epithelial neoplasia TNF
307 G4A
Chlamydia trachomatis
IL10
1117 T4C
Chorioamnionitis
TNF
307 G4A
Chronic alcoholic liver disease
IL10
1117 T4C, IL10
627 C4A, IL10
854 T4C, IL10.G microsat., LTA +252 A4G
Chronic allograft nelphropathy
IL6
174 C4G, MTHFR +677 C4T
Chronic atrophic gastritis/gastric IL1B
511 C4T, IL1RN 86 bp VNTR, TNF
307 G4A
carcinoma
Chronic hepatitis B
IFNG +874 A4T
Chronic hepatitis B virus
LTA +252 A4G, TNF
307 G4A
infection
Chronic hepatitis C
IL1B
511 C4T, TNF
237 G4A
Chronic hepatitis C virus
IL10
1117 T4C, TGFB1 869 C4T, LTA +252 A4G
Chronic immune
LTA +252 A4G
thrombocytopenic purpura
Chronic lung tuberculosis
IL10
1117 T4C, TNF
307 G4A
Chronic obstructive pulmonary
IL10
1117 T4C, TGFB1 869 C4T, LTA +252 A4G
disease
Chronic pelvic pain syndrome
IL10
1117 T4C
Chronic periodontitis
LTA +252 A4G, TNF
307 G4A, IL10
1117 T4C, IL10
627 C4A, IL10
854 T4C, IL2
330 T4G,
IL6
174 C4G, IL6
572 G4C, TGFB1
509 C4T, TNFRSF1B +587 T4G, VDR +352 T4C
Chronic rejection
IL10
1117 T4C, IL1RN 86 bp VNTR, IL4
33 C4T
Chronic schizophrenia
TNF
307 G4A
Coal workers pneumoconiosis
TNF
307 G4A
Coeliac disease
TNF
307 G4A
Colorectal cancer
IL6
174 C4G, IL8
251 T4A, PPARG C4G
Community acquired pneumonia IL10
1117 T4C
Congenital heart block/neonatal TGFB1 869 C4T, TGFB1 915 G4C, TNF
307 G4A
lupus
Contact allergy
IL16
295 T4C
Contact hypersensitivity
TNF
1032 T4C, TNF
863 C4A, TNFd microsat.,
COPD
IL4
33 C4T, IL4
590 C4T, IL4 int3 70 bp VNTR
Coronary artery bypass grafting LTA +252 A4G, TNF
307 G4A
Coronary artery disease
CX37 1019C4T, IL6
174 C4G, MMP3
1171 5A46A, TNF
863 C4A
Coronary artery stenosis
PECAM1 R643G
Coronary atherosclerosis
IL1RN 86 bp VNTR
Coronary function
IL1B
511 C4T
Coronary heart disease
IL10
1117 T4C, IL6
174 C4G, TNF
307 G4A
Cortical bone resorption
IL6
174 C4G
Crohns disease
TNFRSF1B +1466 A4G, TNFRSF1B +1493 C4T, IL16
295 T4C, IL18 +105 A4C, TNF
863 C4A
Cutaneous malignant melanoma TNF
237 G4A, VEGF +405 G4C, VEGF +936 C4T, VEGF
1154 G4A, VEGF
2578 C4A
Cutaneous neonatal lupus
TNF
307 G4A
Cutaneous T-cell lymphoma
IL6
599 A4G
Dementia
TNF
307 G4A, TNF
850 C4T
Dengue fever
TNF
307 G4A, VDR +352 T4C
Dermatomyositis
TNF
307 G4A
Diabetic nephropathy
CCL5
28 C4G, IL1B
511 C4T, IL1RN 86 bp VNTR, IL6
634 C4G
Diarrhea
IL8
251 T4A
Discoid rash
IL4
590 C4T, IL4 int3 70 bp VNTR
Distal gastric cancer
IL1B
31 T4C
Duodenal ulcers
IL1B +3953 C4T, IL1B
31 T4C, IL1B
511 C4T, IL1RN 86 bp VNTR, IL8
251 T4A
Early-onset joint erosions in
LTA +252 A4G, TNF
307 G4A
psoriatic arthritis
Early-onset periodontitis
IL1RN 86 bp VNTR
Eclampsia
TNF
307 G4A
End-stage non-ischemic
TNF
307 G4A
myocardial dysfunction
Endemic pemphigus foliaceus
IL4
590 C4T, IL6
174 C4G
Endometriosis
IFNG intron 1 CA rep., IL10
627 C4A, TNF
1032 T4C, TNF
857 C4T, TNF
863 C4A
End-stage renal disease
CTLA4
318 C4T, IFNG +874 A4T, IL10 GCC4ACC promotor genotype, IL1RN 120 T4C, long CTLA4
ATn repeats
Familial RA
TNFRSF1B +676 G4T
Fasting glycemia lipid parameters LTA +252 A4G, IL10.G microsat.
Fat-free mass
IL6
174 C4G
Carotid plaque
Celiac disease
Cerebral infarction
Cerebral injury
Cerebral malaria
Cervical abormalities
Cervical cancer

Genes and Immunity

Cytokine gene polymorphism in human disease

MV Hollegaard and JL Bidwell

272

Table 1 Continued
Disease

Yes

Febrile convulsion
Febrile seizures
Focal segmental
glomerulosclerosis
Fulminant hepatitis
Gastric adenocarcinoma
Gastric cancer

IL1RN 86 bp VNTR
IL1B
511 C4T
IL10
1117 T4C

Gastric carcinoma
Gastric diseases
Gastric inflammation
Gastric mucosa-associated
lymphoid tissue lymphoma
Gastroesophageal reflux disease
Generalized aggressive
periodontitis
Glaucoma
Glucose tolerance
Glucose-6-phosphate
dehydrogenase deficiency
Graft-versus-host disease
Graves disease
Hematological malignancies:
toxic complications
Hashimoto thyroiditis
Hayfever/atopy
HCV infection
HCV viral clearance
HCV-induced cirrhosis
Heart rate
Helicobacter pylori infection
Helicobacter pylori seropositivity
Helicobacter pylori-associated
diseases
Henoch-Schonlein purpura
Hepatitis B vaccination
Hepatitis B virus

TNF
1032 T4C, TNF
863 C4A

IL1B
31 T4C, iNOS CCTTT pentanucleotide
IL10
1117 T4C, IL1B 1473 C4G, IL1B
31 T4C, IL1B
511 C4T, IL1RN 86 bp VNTR, IL8
251 T4A,
LTA +252 A4G, LTA +804 C4A, MMP1
1607 G del., TNF
1032 T4C, TNF
237 G4A, TNF
307
G4A, TNF
857 C4T, TNF
863 C4A
IL10
1117 T4C, IL10
627 C4A, IL10
854 T4C, IL1B
511 C4T, IL1RN 86 bp VNTR
IL8
251 T4A
IL1B +231, IL1B
511 C4T, IL1RN 86 bp VNTR
TNF
857 C4T, IL1B
31 T4C, IL1RN 86 bp VNTR
IL1B
31 T4C, IL1B
511 C4T, IL1RN 86 bp VNTR
IL1A +4845 G4T, IL1B +3953 C4T, IL1B
511 C4T, IL1RN 86 bp VNTR
TNF
307 G4A, TNF
857 C4T, TNF
863 C4A
IL6
174 C4G
IFNG +874 A4T, IL10
627 C4A, IL6
174 C4G
IL10
627 C4A, TNFRSF1B +676 G4T, IL2
330 T4G, IL1A 46 bp VNTR, IL1A
889 C4T, IFNG +874
A4T, IL10
1117 T4C, IL10
854 T4C, IL1B +3953 C4T, IL6
174 C4G, TNF +488 G4A, TNFd
microsat.
IL13 +2044, IL13
1111 C4T, LTA +252 A4G, TNF
237 G4A, TNF
307 G4A
LTA +252 A4G, TNF
307 G4A
TNF
307 G4A
IL2
330 T4G, IL6
174 C4G
IL10
1117 T4C, IL10
627 C4A, IL10
854 T4C, IL6
174 C4G
IL6
174 C4G, TGFB1 869 C4T, TGFB1 915 G4C
IL1B
511 C4T, IL1RN 86 bp VNTR
IL6
599 A4G
IL10
854 T4C, IL1B
511 C4T, IL8
251 T4A
IL1B
31 T4C
IL1R1 1622 A4G, IFNG +874 A4T, IL10
854 T4C, TNF
857 C4T

TGFB1
509 C4T

IL12B promoter, IL1B +3953 C4T, IL2
330 T4G, IL4
1098 T4G, IL4
33 C4T, IL4
590 C4T
IL10
1117 T4C, IL10
627 C4A, IL10
854 T4C, TNF
1032 T4C, TNF
161 G4A, TNF
237 G4A,
TNF
375 G4A, TNF
307 G4A, TNF
857 C4T, TNF
863 C4A
Hepatitis C virus
IL10
1117 T4C, OPN
443 T4C, TNF
307 G4A, TNF
863 C4A
Hepatitis C virus infection
TNF +1304 A4G, TNF +851 A4G, TNF
1032 T4C, TNF
1073 C4T, TNF
237 G4A, TNF
243
G4A, TNF
307 G4A, TNF
375 G4A, TNF
863 C4A
Hepatocellular carcinoma
IFNG +874 A4T, IL10
1117 T4C, IL10
854 T4C, IL12B
1188 A4C, IL18
137 G4C, IL1RN 86 bp
VNTR, IL2
330 T4G, IL4
590 C4T, IL6
174 C4G, TNF
307 G4A
Herpes zoster
IL10
1117 T4C, IL10
627 C4A, IL10
854 T4C
HIV
IL4
590 C4T
HIV rel. lipodystrophy
TNF
237 G4A, TNF
307 G4A
HIV replication
IL1A
889 C4T
HIV: immune restoration disease IL12B
1188 A4C, IL6
174 C4G, TNF
307 G4A
HIV-1 infection
IL10
627 C4A, IL4
590 C4T, TNF
307 G4A
HIV-1 viremia
TNF
1032 T4C, TNF
863 C4A
Hodgkin lymphoma
IL6
174 C4G, TNFa microsat.
HTLV-I-associated
IL10
627 C4A
myelopathy4tropical spastic
paraparesis
Hyperandrogenism
IL6
174 C4G, IL6
599 A4G
Hypertension
CCR2 +190 G4A, IL1B
31 T4C, TNF
237 G4A
Idiopathic pulmonary fibrosis
TNF
307 G4A
Idiopathic recurrent miscarriage HO-1 GTn microsatellite size
IgA nephropathy
IFNG intron 1 CA rep., IL1B
511 C4T, IL1RN 86 bp VNTR, IL4 int3 70 bp VNTR, TGFB1
509 C4T,
TGFB1 869 C4T, TNF
307 G4A, IL10
1117 T4C
IgE levels
IL4R haplotype 50
478, IL4R haplotype 50
551
Immunosuppressive therapy
TNF
307 G4A
Inflammatory bowel disease
ICAM1 K469E, IL18 +113 T4G, IL18 +127 C4T, IL1RN 86 bp VNTR, TNF
307 G4A, TNF
857 C4T,
TNFRSF1A +36 A4G, TNFRSF1B +587 T4G
Inflammatory stress: fish oil
IL1B
511 C4T, IL6
174 C4G, LTA +252 A4G, TNF
307 G4A
Insulin resistance
TNF
307 G4A, PPARG C4G
Insulin sensitivity
IL6
174 C4G

Genes and Immunity

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MV Hollegaard and JL Bidwell

273

Table 1 Continued
Disease

Yes

Intima-media thickness of the

carotid artery in hypertensive
patients
Ischemic stroke

OPG 950 T4C

Juvenile idiopathic arthritis

Juvenile oligoarthritis
Kaposis sarcoma
Kidney allograft survival
Kidney graft survival
Kidney transplantation
Lacunar infarction
Lacunar stroke
Latent autoimmune diabetes in
adults
Late-onset Alzheimer disease
Leiomyomas
Leishmania chagasi infection
Leprosy
Lipodystrophy
Liver transplants
Lofgrens syndrome
Longevity
Lung cancer
Lung junction
Lupus nephritis
Major depressive disorder
Malaria
Marginal bone loss
Melanoma patients
Meningococcal disease
Microscopic polyangiitis
Migraine
Mixed connective tissue disease
Mortality in patients with severe
sepsis
Multi-infarct dementia
Multiple organ dysfunction
syndrome
Multiple sclerosis

CRP +1059 G4C, ICAM1 K469E, IL1B
511 C4T, IL1RN 86 bp VNTR, IL6
174 C4G, MCP1
2518
A4G, MIF
173 G4C, MMP3
1171 5A46A, TNF
307 G4A
IL13 R110Q, IL1B +3962 T4C, IL4
1098 T4G, IL6
174 C4G, MICA microsat., MIF
173 G4C, TNF

307 G4A, TNFa microsat.
TNF +851 A4G
IL6
174 C4G, IL8
251 T4A, CD14
159 C4T, VEGF
634 C4G
IL6
174 C4G, IL6
599 A4G
TNF
307 G4A
TNF
307 G4A
IL6
174 C4G
IL6
174 C4G
TNF
307 G4A
TNF
307 G4A
TNF
307 G4A
TNF
307 G4A
IL10
2763 C4A, IL10
2849 A4G, IL10
3575 T4A
TNF
237 G4A
TNF
307 G4A
LTA +252 A4G, TNF
307 G4A
IFNG +874 A4T, IL10
1117 T4C, IL10
627 C4A, IL10
854 T4C, IL6
174 C4G, TGFB1 915 G4C,
TNF
307 G4A
IL8
251 T4A
IL10 +1668 A4T
IFNG intron 1 CA rep.
IL1B
511 C4T, MCP1
2518 A4G, TNF
307 G4A
IL12B
1188 A4C, IL12B promoter, IL1A +4845 G4T, IL1B +3953 C4T, IL4 int3 70 bp VNTR, iNOS 954
G4C
IL1B
511 C4T
IFNG +874 A4T, IL10
1117 T4C
IL10
1117 T4C, IL1B
511 C4T, IL1RN +2018 T4C, IL1RN 86 bp VNTR, IL6
174 C4G
IL10
1117 T4C
IL1A
889 C4T, LTA +252 A4G, TNF
307 G4A
MICA microsat., TNF
307 G4A
IL1RN 86 bp VNTR
IL6
174 C4G
IL10
627 C4A

C1_3_2, C1
3
2*354, D6S265, D6S276, IFNG +5644 G4A, IFNG intron 1 CA rep., IL10
1117 T4C,
IL10.G microsat., IL1A
889 C4T, IL1B +1903, IL1B +3876, IL1B +3953 C4T, IL1B
511 C4T, IL1RN
86 bp VNTR, IL4 +2580 C4A, IL4
33 C4T, IL4
590 C4T, IL4 709 VNTR, LTA +252 A4G, MCP3 gene
CA4GA microsatellite, OPN +8090 C4T, OPN +9583 G4A, TNF
307 G4A, TNF
375 G4A, TNFa
microsat., TNFRSF1B +1668 T4G
Multiple system atrophy
IL1A
889 C4T, IL1B
511 C4T, IL8
251 T4A, TNF
1032 T4C
Muscle hypertrophy
IL15RA C4A exon 7
Myasthenia gravis
IL1A
889 C4T
Myelodysplastic syndrome
TNF
307 G4A
Myelopathy
IL6
634 C4G
Myocardial infarction
IL1B
511 C4T, IL6
174 C4G, PECAM1 G670R, PECAM1 N563S, PECAM1 R643G, TNFRSF1A R92Q
Narcolepsy
TNF
857 C4T
Nasal polyposis
IL1A +4845 G4T
Nasopharyngeal carcinoma
HSP70
2 +1267
Necrotizing enterocolitis
IL4R +1902 G4T
Neonatal morbidity
IL1RN 86 bp VNTR
Neonatal sepsis
IL6
174 C4G
Nephropathy
VEGF
2549 18 bp del4ins
Nephrotic syndrome
IL1RN 86 bp VNTR
Non-alcoholic fatty liver
TNF
237 G4A
Non-alcoholic steatohepatitis
IL1B
511 C4T
Non-Hodgkins lymphoma
TNF
307 G4A
Nonimmunologic post-transplant TGFB1 915 G4C, IL10
1117 T4C, IFNG +874 A4T
complications: diabetes
Obesity
IL6
174 C4G, IL6R +3944 T4G, IL6R c_1158918_10, IL6R c_30046_10, IL6R rs1138004, IL6R rs1138006,
TNF
307 G4A
Oesophagitis
IL1B
511 C4T, IL1RN 86 bp VNTR
Oral lichen planus
IFNG +5644 G4A, TNF
307 G4A
Oral submucous fibrosis
TNF
307 G4A

Genes and Immunity

Cytokine gene polymorphism in human disease

MV Hollegaard and JL Bidwell

274

Table 1 Continued
Disease

Yes

Osseointegrated implants
Ossification
Osteoarthritis

IL1A +4845 G4T, IL1B +3953 C4T

IL1B
511 C4T
IL1A
889 C4T, IL1A IVS4 n rep., IL1B +3953 C4T, IL1B
31 T4C, IL1B
511 C4T, IL1B 5810 G4A,
IL1RN +11100 T4C, IL1RN +8006 T4C, IL1RN 86 bp VNTR, IL4R +1124 A4C, IL4R +1232 C4T, IL4R
+148 A4G, IL4R +1682 T4C, IL4R +1902 G4T, IL4R +676 C4T, IL4R
1914, IL4R
3223 C4T, IL4R
S727A
TNF
237 G4A
IL1A
889 C4T, IL1B +3953 C4T
IL1B +3953 C4T, IL6
174 C4G, OPG
223 T4C, TNFRSF1B +593 A +598 T +620 C homozygous
haplotype
IL1RN 86 bp VNTR, IL6
174 C4G
LTA +252 A4G, TNF
1032 T4C, TNF
237 G4A, TNF
307 G4A, TNF
375 G4A

Osteolysis
Osteomyelitis
Osteoporosis
Ovarian cancer
Ozone-induced change in lung
function
Parkinsons disease
Paroxysmal nocturnal
hemoglobinuria aplastic anemia
Patchy alopecia areata
Pemphigus foliaceus
Peri-implant bone loss
Periodontal disease
Periodontitis
Peripheral artery occlusive
disease
Peritoneal adhesions
Peyronies disease
Placental inflammation
Plasmodium falciparum
reinfections
Pneumococcal septic shock
Postoperative complications
PPROM
PR3-ANCA vasculitis
Preeclampsia
Preterm birth
Preterm delivery
Preterm newborns
Preterm premature rupture of
membrane
Primary open-angle glaucoma
Prostate cancer
Psoriasis

Psoriasis vulgaris
Psoriatic arthritis
Pulmonary tuberculosis
Recurrent aphthous stomatitis
Recurrent hepatitis C virus
Recurrent pregnancy loss
Recurrent spontaneous abortion
Reflux nephropathy
Renal allograft rejection
Renal cell carcinoma
Renal parenchymal scarring
Renal transplant outcome
Renovascular disease
Respiratory syncytial virus
Response to early rheumatoid
arthritis treatment
Restenosis
Retinal artery occlusion
Rheumatic heart disease
Rheumatoid arthritis

Genes and Immunity

IL1B
511 C4T, IL6
174 C4G, IL8
251 T4A

IFNG +874 A4T, TGFB1 869 C4T, TGFB1 915 G4C
IL1RN 86 bp VNTR
IL10
854 T4C, IL10 haplotype
10824
819 A4T, TNF
307 G4A
IL1A +4845 G4T, IL1B +3953 C4T
IL1A +4845 G4T, IL1A
889 C4T, IL1B +3953 C4T, IL1RN 86 bp VNTR
IL1A
889 C4T, IL1B +3953 C4T, IL1RN 86 bp VNTR, IL6
174 C4G, TNF
307 G4A
IL6
174 C4G
IL1RN 86 bp VNTR
TGFB1 915 G4C
LTA +252 A4G, TNF
237 G4A
TNF
307 G4A
IL10
1117 T4C
LTA +252 A4G
Homozygosity for IL10
1082G4
819C4
592C haplotype
IL1B +3953 C4T, IL1RN 86 bp VNTR
IL1RN 86 bp VNTR, TNF
850 C4T
IL10 haplotype
1082A4
819T4
592A, IL1RN 86 bp VNTR, IL4
590 C4T, IL6
174 C4G, MBL2
G54D, TNF haplotype+488A4
238G4
308G
ACE int.16 ins./del., IL1B +3953 C4T, IL1RN 86 bp VNTR, MTHFR +677 C4T, TNF
863 C4A
IL1RN 86 bp VNTR
IL1RN 86 bp VNTR, HSP70
2 +1267, TNF
307 G4A
IL1B +3953 C4T, TNF
307 G4A
IL1B +3953 C4T
CDSN +1243 C4T, CDSN +619 T4C, IL10
1117 T4C, IL10
627 C4A, IL19 rs2073186, IL19 rs2243174,
IL19 rs2243188, IL19 rs2243191, IL19 rs2243193, IL1B
511 C4T, IL20
1053 T4G, IL20 gene rs2981572,
IL20 rs2232360, IL20 rs2981573, LTA +252 A4G, MIF
173 G4C, MIF
714 tetra nucleotide repeat, TNF

237 G4A
IL12B
1188 A4C
MICA microsat., MICB microsat., TNF
237 G4A, TNF
307 G4A
IL10
1117 T4C, TNF
307 G4A
IL1B
511 C4T, IL1RN 86 bp VNTR, IL6
174 C4G
IFNG +874 A4T
IFNG +874 A4T, IL10
1117 T4C, IL1B
31 T4C, IL1B
511 C4T, IL6
634 C4G
IL1RN 86 bp VNTR, IL6
174 C4G
TNF
307 G4A
TGFB1 869 C4T, TGFB1 915 G4C, TNF
307 G4A
IL10
1117 T4C
TGFB1
509 C4T, TGFB1
800 G4A, TGFB1 869 C4T
IL2
330 T4G
IL10
1117 T4C, IL10
627 C4A, IL10
854 T4C
IL10
627 C4A, IL4
590 C4T, IL4R +148 A4G, IL4R +1902 G4T
LTA +252 A4G, LTA +365 G4C, LTA +720 C4A, TNF +488 G4A, TNF
237 G4A, TNF
307 G4A
IL1B
511 C4T, IL1RN 86 bp VNTR, IL6
174 C4G
IL6
174 C4G
TNF
237 G4A, TNF
307 G4A
24 microsatelites, BAT2 microsat., CTLA4 n microsat., D6S2222, D6S2223, D6S273, IL10
1117 T4C, IL10

2849 A4G, IL10.G microsat., IL1B +3953 C4T, IL1RN +2018 T4C, IL1RN 86 bp VNTR, LTA +252
A4G, TGFB1 915 G4C, TNF +1304 A4G, TNF +488 G4A, TNF +851 A4G, TNF
1032 T4C, TNF

237 G4A, TNF
307 G4A, TNF
863 C4A, TNFa microsat., TNFb TNFc TNFd TNFe D6S273, TNFd
microsat., TNFRSF1A +36 A4G, TNFRSF1B +676 G4T, TNFRSF1B microsat., VEGF +936 C4T, VEGF

1154 G4A, VEGF
2578 C4A, VEGF
634 C4G

Cytokine gene polymorphism in human disease

MV Hollegaard and JL Bidwell

275

Table 1 Continued
Disease

Yes

Sarcoidosis

CCL5
403 G4A, IFNG intron 1 CA rep., IL18
137 G4C, IL18
607 C4A, IL1A
889 C4T, TNF
857
C4T
CTLA4 +49 A4G, IL10
627 C4A, IL10 GCC homozygotes, IL1B
511 C4T, IL1RN 86 bp VNTR, LTA
+252 A4G, TNF
307 G4A
TNF
863 C4A
IL10
137 G4C, IL10
627 C4A, IL1RN 86 bp VNTR, LTA +252 A4G
TNF
307 G4A
HSP70
2 +1267, LTA +252 A4G, TNF
307 G4A
IL6
174 C4G
CD14
159 C4T
TNF
307 G4A, TNF
1032 T4C, TNF
857 C4T, TNF
863 C4A
IL1B
511 C4T
TNF
307 G4A
IL10
1117 T4C
IL1RN 86 bp VNTR
IL1B
511 C4T
IFNG +2109 A4G, IFNG +3810 G4A
IL1B +3953 C4T
IL10
1117 T4C, TLR4 +896 A4G, TNF
307 G4A
TNF
237 G4A, TNF
307 G4A, TNF
375 G4A
IL6
174 C4G
MCP1
2518 A4G

Schizophrenia
Scleroderma
Sepsis
Sepsis mortality
Septic shock
Septicemia
Serum lipoproteins
Severe acute pancreatitis
Severe Alzheimers
Severe aplastic anemia
Severe chronic periodontitis
Severe dementia
Severe gastric inflammation
Severe hepatic fibrosis
Severe rheumatoid arthritis
Severe sepsis
Severe silicosis
Severe stroke
Severity of HCV-related liver
disease
Sjogrens syndrome
Smoking
Spondyloarthropathy
Spontaneous abortions
Spontaneous preterm birth
Stroke
Subacute sclerosing
panencephalitis
Sudden infant death syndrome
Synthetic hemodialysis graft
failure
Systemic lupus erythematosus

Systemic lupus erythematosus

Systemic sclerosis
Transplant-related mortality
Tuberculosis
Type I diabetes mellitus

Type II diabetes mellitus

Ulcerative colitis
Unstable angina
Urinary tract infection
UVB-induced
immunomodulation
Vaginal immune defense
Vascular morphology
Viral hepatitis C
Vulvar carcinogenesis
Vulvar vestibulitis syndrome
Waist-to-hip ratio
Wegeners granulomatosis

CCR5 32-bp del., TNF
307 G4A, IL1B
31 T4C, IL1B 3877, IL1B
511 C4T
mono-S-RCCX-TNF2 haplotype, IL6
174 C4G
CD14
159 C4T
IL1RN 86 bp VNTR
IL4
590 C4T, TNF
307 G4A, IL6
174 C4G
IL4
590 C4T, PAI1 +11053 T4G
IL4
590 C4T
IL6 1753 C4G, IL6
174 C4G, IL6 2954 G4C haploypes
TNF
307 G4A
C4AQ0, CCL5
28 C4G, IL10
1117 T4C, IL10 Haplotype
3575 T
2763C
1082A
819 T
592A,
IL1A +4845 G4T, IL1A
889 C4T, IL1B +3953 C4T, IL1B
511 C4T, IL1RN 86 bp VNTR, IL8
845
T4C, MBL2 G57E, MBL2
221 X4Y, MBL2
550 H4L, MBL2 G54D, MBL2 R52C, MCP1
2518 A4G,
OPN +1239 A4C, OPN
156 G del., TNF
307 G4A
TNF
307 G4A
IL1A +4729 T4C, IL1A +4845 G4T, IL1A
889 C4T, MCP1
2518 A4G
IL10
1117 T4C, IL10
627 C4A, IL10
854 T4C, TNF
1032 T4C, TNF
237 G4A, TNF
307 G4A,
TNFa microsat., TNFd microsat., TNFd microsat.
IL12B int. 2 ATT, IL12B promoter, intron 2, intron 4, 30 UTR haplotypes, IL12RB1 haplotype 2: 641G 684 T
1094C 1132C, TNF
237 G4A, TNF
307 G4A
IL10
1117 T4C, IL10
627 C4A, IL10
854 T4C, IL12B int. 2 ATT, IL12B +1159 C4A, IL4R +1124
A4C, IL4R +1417 G4T, IL4R +1466 T4C, IL4R +148 A4G, IL4R +1682 T4C, IL4R +1902 G4T, IL4R
+676 C4T, IL4R
3223 C4T, IL4R S761P haplotypes, TNF
307 G4A, TNF microsat., IL1B +3953 C4T,
IL6
174 C4G, IL18
137 G4C, IL18
607 C4A, TNFRSF1A
383 A4C
APM1 haplotype
11391
11377, IL6R +48867 A4C, TNF
307 G4A, IL6
174 C4G, TNF
863 C4A,
CD14
159 C4T
IL11.A142 dinucleotide rep., IL1RN 86 bp VNTR, MIF
173 G4C, TNF
237 G4A, TNF
307 G4A
TNF
307 G4A
LTA +365 G4C, TNF
237 G4A
IL1B +3953 C4T
TLR4 +896 A4G
OPG 950 T4C
TNF
307 G4A
IL1RN 86 bp VNTR
IL1B +3953 C4T, IL1RN 86 bp VNTR
LTA +252 A4G, TNF
307 G4A
IL10
1117 T4C, IFNG +874 A4T, TNF
237 G4A

displayed on the web pages, although grouped fairly

conveniently into by gene and by disease pages, and
with separate pages for TNF superfamily and for other
entries, cannot be sorted further by the user within the

site. For this reason, separate and sortable copies of the

database are supplied in Microsoft Excel spreadsheet
format, available from the download page. Searches
within the website for individual genes, polymorphisms
Genes and Immunity

Cytokine gene polymorphism in human disease

MV Hollegaard and JL Bidwell

276

Figure 1 Screenshot from the Links Navigator page on the Cytokine Gene Polymorphism in Human Disease website showing a part of the
new design.

or diseases can however be accomplished in a web

browser by using the Edit. Find (on This Page) menu
command.

References
1 Bidwell J, Keen L, Gallagher G, Kimberly R, Huizinga T,
McDermott MF et al. Cytokine gene polymorphism in human
disease: on-line databases. Genes Immun 1999; 1: 319.
2 Bidwell J, Keen L, Gallagher G, Kimberly R, Huizinga T,
McDermott MF et al. Cytokine gene polymorphism in human

Genes and Immunity

disease: on-line databases. Genes Immun 2001; 2 (Suppl 1):

6170.
3 Haukim N, Bidwell JL, Smith AJ, Keen LJ, Gallagher G,
Kimberly R et al. Cytokine gene polymorphism in human
disease: on-line databases. Genes Immun 2002; 3 (Suppl 2):
313330.
4 Hinrichs AS, Karolchik D, Baertsch R, Barber GP, Bejerano
G, Clawson H et al. The UCSC genome browser database: update 2006. Nucleic Acids Res 2006; 34 (Database issue):
D590D598.
5 Riva A, Kohane IS. A SNP-centric database for the investigation of the human genome. BMC Bioinformatics 2004;
5: 33.