PPAR
Crohn’s disease (CD) and ulcerative colitis (UC) are chronic recurrent forms of inflammation of the gastrointestinal tract (inflammatory bowel disease, or IBD), which are characterized by an onset in young adulthood and by an unpredictable disease course that may lead to debilitating complications [
It has been recognized that components of pro- and anti-inflammatory signalling cascades seem to play an important role in the pathogenesis of IBD. Initially, pro- and anti-inflammatory cytoplasmic receptors that are activated by bacterial lipopolysaccharides, such as nucleotide oligomerisation domain (NOD) 2/caspase recruitment domain (CARD) 15, and NOD1/CARD4, have been especially studied in the past and have been identified as IBD susceptibility genes. These findings emphasized the pivotal role of an interaction between enteric microbes and the intestinal immune system in the pathophysiology of IBD [
Current evidence suggests that an additional receptor, PPAR
PPAR
In the present study, we aimed at determining all occurring mutations and SNPs in the exonic regions of the
Two hundred and eighty-four clinically diagnosed Swiss IBD patients (140 UC and 144 CD patients) were recruited at the centers participating in the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS) [
Demographic characteristics of IBD patients and non-IBD controls.
Patient cohort | |||
UC | CD | IBD total | |
140 (49.3) | 144 (50.7) | 284 (100) | |
Male/female | 77 (54.6)/64 (45.4) | 77 (55)/63 (45) | 140 (49.3)/144 (50.7) |
Age at enrolment | |||
Disease location | Available for 110 UC patients: | Available for 125 CD patients (Montreal classification) | |
E1: 11 (10%) | L1: 33 (26.4%) | ||
E2: 58 (52.7%) | L2: 42 (33.6%) | ||
E3: 41 (37.3%) | L3: 46 (36.8%) | ||
L4: 4 (3.2%) | |||
EIM frequency | Available for 139 UC patients: | Available for 142 CD patients: | Available for 281 IBD patients: |
51 (36.7) | 72 (50.7) | 123 (43.8) | |
Fistula frequency | Available for 140 UC patients: | Available for 144 CD patients: | Available for 284 IBD patients: |
10 (7.1) | 73 (50.7) | 83 (29.2) | |
Mean CDAI at enrolment | NA | Available for 127 CD patients: | NA |
State of CD (quiescent/acute) | NA | Available for 127 CD pat.: | NA |
95 (74.8)/32 (25.2) | |||
Mean mtwsi at enrolment | Available for 140 UC patients: | NA | NA |
State of UC (inactive/active) | 118 (84.3)/22 (15.7) | NA | NA |
Leucocytes at enrolment | Valid for 134 UC patients: | Available for 142 CD patients: | Available for 276 IBD patients: |
CRP at enrolment | Valid for 127 CD patients: | Available for 138 CD patients: | Available for 265 IBD patients: |
Control cohort | |||
Control total | |||
194 (100) | |||
Male/female | 77 (39.7)/117 (60.3) | ||
Age at enrolment |
One hundred and ninety-four non-IBD controls were recruited from gastroenterological patients undergoing surveillance colonoscopy, who did not show any symptoms of IBD. History of colorectal cancer was used as an exclusion criterion for both IBD patients and non-IBD controls. All subjects provided their written informed consent to be included in the study. Ethical approvals were obtained from the local medical ethical committees of all study sites involved in the collection of non-IBD samples.
DNA was extracted from EDTA-blood or intestinal biopsies using the QIAcube robotic workstation and a standard procedure (QIAamp DNA Mini Kit, QIAGEN, Switzerland). The PCR and sequencing primer design was based on the NCBI reference sequence for
To detect differences in SNP distribution between case and control groups or between disease activity groups, the Chi-Square test or the Fisher’s exact test was used. A
The FAMHAP software was used to calculate the haplotypes and diplotypes based on the detected SNPs and mutations in the
Linkage disequilibria (LD) were calculated using the
DNA samples from 284 IBD patients (CD or UC) and 194 healthy controls were initially sequenced for the seven
The sequence data were screened for genetic variation in the
Genetic variants detected in
SNP no. | Position in DNA( a) | Exon/ intron no. | Exon position | Intron/ exon | Base exchange | Position in RNA(b) | AA exchange(c) | SNP database |
---|---|---|---|---|---|---|---|---|
1 | 12332979 | 1 | Intron | G>T | NA | Not found | ||
2 | 12333068 | 1 | Exon | insC | 68 | frame shift | Not found | |
3 | 12333070 | 1 | 5-prime | C>T | 70 | 5-prime | Not found | |
4 | 12333125 | 1 | 12333001–12333173 | Exon | C>G | 125 | 12 P [Pro]>A [Ala] | rs1801282 |
5 | 12333199 | 1 | Intron | T>G | NA | Not found | ||
6 | 12333213 | 1 | Intron | G>A | NA | Not found | ||
7 | 12361272 | 2 | 12361203–12361430 | Exon | C>T | 243 | 51 S [Ser]>F [Phe] | Not found |
8 | 12361422 | 2 | Exon | A>G | 393 | 101 E [Glu]>G [Gly] | Not found | |
9 | 12363017 | 3 | 12362821–12362990 | Intron | A>G | NA | Not found | |
10 | 12374014 | 4 | Intron | G>T | NA | Not found | ||
11 | 12374024 | 4 | Intron | A>T | NA | Not found | ||
12 | 12374091 | 4 | Intron | C>A | NA | rs4135333 | ||
13 | 12374110 | 4 | Intron | C>T | NA | Not found | ||
14 | 12374272 | 4 | 12374113–12374251 | Intron | A>T | NA | rs4135334 | |
15 | 12374352 | 4 | Intron | C>T | NA | Not found | ||
16 | 12387616 | 5 | 12387381–12387580 | Intron | G>A | NA | Not found | |
17 | 12398613 | 6 | 12398203–12398653 | Exon | C>T | 1321 | 410 S [Ser]>S [Ser] | Not found |
18 | 12415473 | 7 | Exon | G>A | 1438 | 449 L [Leu]>L [Leu] | Not found | |
19 | 12415557 | 7 | 12415397–12415855 | Exon | C>T | 1522 | 477 H [His]>H [His] | rs3856806 |
20 | 12415581 | 7 | Exon | G>A | 1546 | 485 K [Lys]>K [Lys] | Not found | |
21 | 12415647 | 7 | Exon | G>A | 1611 | 506 stop>stop | Not found | |
22 | 12415669 | 7 | 3′ end | C>T | 3′ end | Not found |
no.: number; AA: amino acid; (a)DNA reference sequence NT_02257.18; (b)RNA reference sequence NM_015869.4; (c)protein reference sequence P37231 (PPARG_HUMAN) SWISSPROT database.
Allele frequencies in IBD cases and healthy controls.
SNP no. | Position in NT_02257.18* | IBD cases | Controls | ||||
---|---|---|---|---|---|---|---|
Allele frequency in % | Allele frequency in % | ||||||
1 | 12332979G>T | 566 | 0 | 0 | 364 | 1 | 0.27 |
2 | 12333068insC | 566 | 1 | 0.18 | 364 | 0 | 0 |
3 | 12333070C>T | 566 | 0 | 0 | 364 | 2 | 0.55 |
4 | 12333125C>G | 566 | 60 | 10.60 | 364 | 50 | 13.74 |
5 | 12333199T>G | 566 | 1 | 0.18 | 364 | 0 | 0 |
6 | 12333213G>A | 566 | 0 | 0 | 364 | 3 | 0.82 |
7 | 12361272C>T | 562 | 1 | 0.18 | 358 | 0 | 0 |
8 | 12361422A>G | 562 | 0 | 0 | 358 | 1 | 0.28 |
9 | 12363017A>G | 554 | 1 | 0.18 | 334 | 0 | 0 |
10 | 12374014G>T | 554 | 1 | 0.18 | 348 | 0 | 0 |
11 | 12374024A>T | 564 | 1 | 0.18 | 348 | 0 | 0 |
12 | 12374091C>A | 554 | 1 | 0.18 | 348 | 0 | 0 |
13 | 12374110C>T | 554 | 1 | 0.18 | 348 | 0 | 0 |
14 | 12374272A>T | 554 | 1 | 0.18 | 348 | 1 | 0.29 |
15 | 12374352C>T | 554 | 0 | 0 | 348 | 1 | 0.29 |
16 | 12387616G>A | 562 | 1 | 0.18 | 360 | 0 | 0 |
17 | 12398613C>T | 546 | 0 | 0 | 370 | 1 | 0.27 |
28 | 12415473G>A | 546 | 0 | 0 | 350 | 1 | 0.29 |
19 | 12415557C>T | 546 | 66 | 12.09 | 350 | 46 | 13.14 |
20 | 12415581G>A | 546 | 0 | 0 | 350 | 1 | 0.29 |
21 | 12415647G>A | 546 | 2 | 0.37 | 350 | 0 | 0 |
22 | 12415669C>T | 546 | 0 | 0 | 350 | 1 | 0.29 |
no.: number;
The two most often occurring variants
The LD plot for all
As shown in Table
Table
Number of variant carriers in IBD and in non-IBD controls.
SNP | SNP carriers in IBD | SNP carriers in controls | OR (CI) | |||
---|---|---|---|---|---|---|
12332979G>T | 283 | 0 (0) | 182 | 1 (0.5) | NA | 0.39 |
12333068insC | 283 | 1 (0.4) | 181 | 0 (0) | NA | 0.61 |
12333070C>T | 283 | 0 (0) | 181 | 1 (0.6) | NA | 0.39 |
12333125A>G | 283 | 58 (20.5) | 182 | 48 (26.4) | 0.72 | 0.14(b), (c) |
12333125A>G | 227 | Hom only: 2 (0.9) | 136 | Hom only: 2 (1.5) | 0.60 | 0.63(c) |
12333199T>G | 283 | 1 (0.4) | 181 | 0 (0) | NA | 0.61 |
12333213G>A | 283 | 0 (0) | 182 | 3 (1.6) | NA | 0.06 |
12361272C>T | 281 | 1 (0.4) | 179 | 0 (0) | NA | 0.61 |
12361422A>G | 281 | 0 (0) | 179 | 1 (0.6) | NA | 0.39 |
12363017A>G | 277 | 1 (0.4) | 167 | 0 (0) | NA | 0.62 |
12374014G>T | 280 | 1 (0.4) | 174 | 0 (0) | NA | 0.62 |
12374024A>T | 280 | 1 (0.4) | 174 | 0 (0) | NA | 0.62 |
12374091C>A | 280 | 1 (0.4) | 174 | 0 (0) | NA | 0.62 |
12374110C>T | 280 | 1 (0.4) | 174 | 0 (0) | NA | 0.62 |
12374272A>T | 280 | 1 (0.4) | 174 | 1 (0.6) | 0.62 | 0.62 |
12374352C>T | 280 | 0 (0) | 174 | 1 (0.4) | NA | 0.38 |
12387616G>A | 282 | 1 (0.4) | 179 | 0 (0) | NA | 0.61 |
12398613C>T | 281 | 0 (0) | 185 | 1 (0.5) | NA | 0.40 |
12415473G>A | 273 | 0 (0) | 175 | 1 (0.6) | NA | 0.39 |
12415557C>T | 273 | 63 (23.1) | 175 | 42 (24) | 0.95 | 0.82(b ), (c) |
12415557C>T | 213 | Hom only: 3 (1.4) | 137 | Hom only: 4 (2.9) | 0.48 | 0.44(c) |
12415581G>A | 273 | 0 (0) | 175 | 1 (0.6) | NA | 0.39 |
12415647G>A | 273 | 2 (0.7) | 175 | 0 (0) | NA | 0.37 |
12415669C>T | 273 | 0 (0) | 175 | 1 (0.6) | NA | 0.39 |
OR: odds ratio; CI: confidence interval; no.: number;
Number of variant carriers (12333125A>G and 12415557C>T) in CD and UC patients compared to controls.
Category | 12333125A>G | ||||||
---|---|---|---|---|---|---|---|
Genotype | OR (C.I.) | OR (C.I) (b) | |||||
CD | Het plus hom | 143 | 28 (19.6) | 0.68 (0.40–1–15) | 0.15(d) | 0.67 (0.40–1.14) | 0.14 |
control | Het plus hom | 182 | 48 (26.4) | ||||
CD | hom | 116 | 1 (0.9) | 0.58 (0.05–6.51) | 1.0 | 0.77 (0.23–2.61) | 0.68 |
control | hom | 136 | 2 (1.5) | ||||
UC | Het plus hom | 140 | 30 (21.4) | 0.76 (0.45–1.28) | 0.31(d) | 0.78 (0.46–1.32) | 0.35 |
control | Het plus hom | 182 | 48 (26.4) | ||||
UC | hom | 111 | 1 (0.9) | 0.61 (0.06–6.81) | 1.0 | 0.70 (0.21–2.38) | 0.57 |
control | hom | 136 | 2 (1.5) | ||||
12415557C>T | |||||||
CD | Het plus hom | 139 | 31 (22.3) | 0.91 (0.54–1.54) | 0.72(d) | 0.92 (0.54–1.56) | 0.74 |
control | Het plus hom | 175 | 42 (24.0) | ||||
CD | hom | 109 | 1 (0.9) | 0.31 (0.03–2.80) | 0.39 | 0.54 (0.18–1.62) | 0.27 |
control | hom | 137 | 4 (2.9) | ||||
UC | Het plus hom | 134 | 32 (23.9) | 0.99 (0.59–1.68) | 0.98(d) | 0.94 (0.55–1.62) | 0.83 |
control | Het plus hom | 175 | 42 (24.0) | ||||
UC | hom | 104 | 2 (1.9) | 0.65 (0.12–3.63) | 0.70 | 0.84 (0.35–1.99) | 0.69 |
control | hom | 137 | 4 (2.9) |
OR: odds ratio; CI: confidence interval;
Impact of variant 12333125A>G on disease activity.
Category | 12333125A>G | ||||||
---|---|---|---|---|---|---|---|
Genotype | OR (C.I.) | OR (C.I.) (b) | |||||
Fistula | Het plus hom | 83 | 15 (18.1) | 1.24 (0.64–2.39) | 0.52 | 1.25 (0.65–2.4) | 0.51 |
No Fistula | Het plus hom | 200 | 43 (21.5) | ||||
Fistula | hom | 68 | 0 (0.0) | NA | 1(c) | NA | 1 |
No Fistula | hom | 159 | 2 (1.3) | ||||
EIM | Het plus hom | 122 | 23 (18.9) | 1.23 (0.68–2.21) | 0.5 | 1.22 (0.67–2.21) | 0.51 |
No EIM | Het plus hom | 158 | 35 (22.2) | ||||
EIM | hom | 100 | 1 (1.0) | 0.81 (0.05–13.03) | 1(c) | 0.87 (0.22–3.54) | 0.85 |
No EIM | hom | 124 | 1 (0.8) | ||||
Nonactive UC | Het plus hom | 118 | 26 (22.0) | 0.79 (0.25–2.53) | 0.79 | 0.89 (0.27–2.96) | 0.85 |
active UC(d) | Het plus hom | 22 | 4 (18.2) | ||||
NonActive UC | hom | 93 | 1 (1.1) | NA | 1(c) | NA | 1 |
active UC | hom | 18 | 0 (0.0) | ||||
Quiescent CD | Het plus hom | 94 | 17 (18.1) | 1.51 (0.58–3.93) | 0.4 | 1. 47 (0.56–3.88) | 0.44 |
Acute CD(d) | Het plus hom | 32 | 8 (25.0) | ||||
Quiescent CD | hom | 78 | 1 (1.3) | NA | 1(c) | NA | 1 |
Acute CD | hom | 24 | 0 (0.0) |
Impact of variant 12415557C>T on disease activity.
Category | 12415557C>T | ||||||
---|---|---|---|---|---|---|---|
Genotype | OR (C.I.) | OR (C.I.) (b) | |||||
Fistula | Het plus hom | 79 | 18 (22.8) | 1.02 (0.55–1.9) | 0.94 | 1.04 (0.56–1.95) | 0.89 |
No Fistula | Het plus hom | 194 | 45 (23.2) | ||||
Fistula | hom | 62 | 1 (1.6) | 0.89 (0.07–9.2) | 1(c) | 0.89 (0.26–3.01) | 0.85 |
No Fistula | hom | 151 | 2 (1.3) | ||||
EIM | Het plus hom | 116 | 26 (22.4) | 1.10 (0.62–1.94) | 0.76 | 1.09 (0.61–1.93) | 0.78 |
No EIM | Het plus hom | 154 | 37 (24.0) | ||||
EIM | hom | 92 | 2 (2.2) | 0.39 (0.03–4.31) | 0.58 | 0.65 (0.19–2.2) | 0.49 |
No EIM | hom | 118 | 1 (0.8) | ||||
Nonactive UC | Het plus hom | 114 | 28 (24.6) | 0.77 (0.24–2.49) | 0.78 | 0.89 (0.27–2.99) | 0.86 |
active UC | Het plus hom | 20 | 4 (20.0) | ||||
Nonactive UC | hom | 87 | 1 (1.1) | 5.30 (0.32–90–42) | 0.3 | 3.28 (0.74–14.49) | 0.12 |
active UC | hom | 17 | 1 (5.9) | ||||
Quiescent CD | Het plus hom | 91 | 21 (23.1) | 1.16 (0.45–2.97) | 0.76 | 1.22 (0.47–3.17) | 0.68 |
Acute CD | Het plus hom | 31 | 25.8 (31) | ||||
Quiescent CD | hom | 71 | 1 (1.4) | NA | 1(c) | NA | 1 |
Acute CD | hom | 23 | 0 (0) |
Haplotype and diplotype distribution in IBD cases and non-IBD controls.
Subjects included | H1 (CC)(a) | H2 (CT) | H3 (GC) | H4 (GT) | ||
---|---|---|---|---|---|---|
IBD | 256 | 436.3 (85.2) | 41.3 (8.1) | 12.7 (2.5) | 21.7 (4.2) | 0.23 |
OR (C.I.) | 1.27 (0.87–1.86) | 0.86 (0.52–1.42) | 0.5 (0.23–1.07) | 1.1 (0.53–2.28) | ||
UC | 126 | 212.6 (84.4) | 22.6 (9) | 6.4 (2.5) | 10.4 (4.1) | 0.52 |
OR (C.I.) | 1.19 (0.76–1.87) | 0.96 (0.54–1.72) | 0.51 (0.2–1.3) | 1.07 (0.45–2.51) | ||
CD | 130 | 223.6 (86) | 18.6 (7.2) | 6.4 (2.5) | 11.4 (4.4) | 0.31 |
OR (C.I.) | 1.36 (0.86–2.15) | 0.75 (0.41–1.39) | 0.49 (0.19–1.26) | 1.13 (0.49–2.6) | ||
Controls | 148 | 242.5 (81.9) | 27.5 (9.3) | 14.5 (4.9) | 4.5 (3.9) | |
D1 (CC/CC) (b) | D2 (CC/GT) | D3 (CC/GC) | D4 (CC/CT) | |||
IBD | 256 | 184.0 (71.9) | 37.3 (14.6) | 12.0 (4.7) | 19.0 (7.4) | |
OR (C.I.) | 1.3 (0.84–2.02) | 0.86 (0.49–1.5) | 0.51 (0.23–1.15) | 1.24 (0.55–2.81) | ||
UC | 126 | 89.0 (70.6) | 19.6 (15.6) | 6.0 (4.8) | 9.0 (7.1) | |
OR (C.I.) | 1.23 (0.73–2.05) | 0.93 (0.49–1.78) | 0.52 (0.19–1.41) | 1.19 (0.46–3.09) | ||
CD | 130 | 95.0 (73.1) | 17.6 (13.5) | 6.0 (4.6) | 10.0 (7.7) | |
OR (C.I.) | 1.39 (0.83–2.32) | 0.79 (0.41–1.54) | 0.5 (0.19–1.36) | 1.29 (0.51–3.27) | ||
Controls | 148 | 98.0 (66.2) | 24.5 (16.6) | 13.0 (8.8) | 9.0 (6.1) | |
D5 (CT/GT) | D6 (GC/GT) | D7 (GC/CT) | D8 (GT/GT) | |||
IBD | 2.0 (0.8) | 0.0 (0) | 0.7 (0.3) | 1.0 (0.4) | 0.409 | |
OR (C.I.) | 0.58 (0.08–4.12) | — | — | — | ||
UC | 1.0 (0.8) | 0.0 (0) | 0.0 (0) | 1.0 (0.8) | 0.716 | |
OR (C.I.) | — | — | — | |||
CD | 0.0 (0) | 0.0 (0) | 0.0 (0) | 0.0 (0) | 0.588 | |
OR (C.I.) | — | — | — | |||
Controls | 2.0 (1.4) | 1.0 (0.7) | 0.5 (0.3) (d) | 0.0 (0) |
OR: odds ratio; CI: confidence interval;
Furthermore a comparison of the mean values of leukocyte or CRP concentrations in plasma did not show any significant differences between IBD patients carrying the variant
The two
Neither the overall haplotype nor the overall diplotype pattern varied significantly between the IBD group (or the IBD subgroups) and the control group. The result remained non-significant when investigating a possible relationship between the occurring haplotype or diplotype distribution pattern and disease activity (abundance of EIMs, fistulas, or high activity indices; Tables
Haplotype and diplotype distribution in IBD cases with and without EIMs.
Subjects included | H1 (CC) | H2 (CT) | H3 (GC) | H4 (GT) | ||
---|---|---|---|---|---|---|
IBD | 110 | 189.8 (86.2) | 10.2 (4.6) | 3.2 (1.5) | 16.8 (7.6) | 0.57 |
OR (CI) | 1.18 (0.72–1.95) | 1.18 (0.50–2.80) | 0.44 (0.12–1.58) | 0.87 (0.46–1.67) | ||
Controls(b) | 143 | 240.7 (84.1) | 11.4 (4.0) | 9.3 (3.3) | 24.7 (8.6) | |
UC | 45 | 76.9 (85.5) | 5.1 (5.6) | 1.1 (1.2) | 6.9 (7.7) | 0.55 |
OR (CI) | 1.15 (0.56–2.37) | 1.79 (0.51–6.25) | 0.36 (0.04–2.93) | 0.76 (0.3–1.93) | ||
Controls(b) | 80 | 133.8 (83.6) | 5.2 (3.2) | 5.2 (3.2) | 15.8 (9.9) | |
CD | 65 | 112.8 (86.8) | 5.2 (4.0) | 2.2 (1.7) | 9.8 (7.6) | 0.82 |
OR (CI) | 1.18 (0.58–2.38) | 0.8 (0.24–2.66) | 0.49 (0.09–2.61) | 1.09 (0.42–2.79) | ||
Controls(b) | 63 | 106.8 (84.8) | 6.2 (4.9) | 4.2 (3.3) | 8.8 (7.0) | |
D1 (CC/CC) | D2 (CC/GT) | D3 (CC/GC) | D4 (CC/CT) | |||
IBD | 110 | 82.0 (74.5) | 14.8 (13.4) | 3.0 (2.7) | 8.0 (7.3) | |
OR (CI) | 1.30 (0.75–2.27) | 0.82 (0.41–1.67) | 0.42 (0.11–1.58) | 0.94 (0.37–2.43) | ||
Controls(b) | 143 | 99.0 (69.2) | 22.7 (15.8) | 9.0 (6.3) | 11.0 (7.7) | |
UC | 45 | 33.0 (73.3) | (13.2) | 1.0 (2.2) | 4.0 (8.9) | |
OR (CI) | 1.25 (0.55–2.82) | 0.73 (0.26–2.06) | 0.34 (0.04–3.01) | 1.46 (0.37–5.75) | ||
Controls(b) | 80 | 55.0 (68.8) | 13.8 (17.3) | 5.0 (6.3) | 5.0 (6.3) | |
CD | 65 | 49.0 (75.4) | 8.8 (13.6) | 2.0 (3.1) | 4.0 (6.2) | |
OR (CI) | 1.32 (0.61–2.88) | 0.96 (0.35–2.63) | 0.47 (0.08–2.65) | 0.62 (0.17–2.32) | ||
Controls(b) | 63 | 44.0 (69.8) | 8.8 (14.0) | 4.0 (6.3) | 6.0 (9.5) | |
D5 (CT/GT) | D6 (GC/GT) | D7 (GC/CT) | D8 (GT/GT) | |||
IBD | 2.0 (1.8) | NP | NP | 0.0 (0) | 0.36 | |
OR (CI) | — | — | ||||
Controls | 0.0 (0) | NP | NP | 1.0 (0.7) | ||
UC | 1.0 (2.2) | NP | NP | 0.0 (0) | 0.6 | |
OR (CI) | — | — | ||||
Controls | 0.0 (0) | NP | NP | 1.0 (1.3) | ||
CD | 1.0 (1.5) | NP | NP | NP | 0.73 | |
OR (CI) | — | |||||
Controls | 0.0 (0) | NP | NP | NP |
OR: odds ratio; CI: confidence interval;
Haplotype and diplotype distribution in IBD cases with and without fistulas.
Subjects included | H1 (CC) | H2 (CT) | H3 (GC) | H4 (GT) | ||
---|---|---|---|---|---|---|
IBD | 77 | 132.9 (86.3) | 7.1 (4.6) | 3.1 (2.0) | 10.9 (7.0) | 0.89 |
OR (C.I.) | 1.13 (0.65–1.94) | 1.16 (0.46–2.9) | 0.77 (0.21–2.81) | 0.81 (0.40–1.67) | ||
Controls (b) | 179 | 303.6 (84.8) | 14.4 (4.0) | 9.4 (2.6) | 30.6 (8.5) | |
UC | 9 | 17.0 (94.4) | 0.0 (0.001) | 0.0 (0.001) | 1.0 (5.5) | 0.65 |
OR (C.I.) | 0.02 (0.0–439897.28) | 0.03 (0.0–739520.9) | 0.57 (0.07–4.52) | |||
Controls (b) | 117 | 195.8 (83.7) | 10.2 (4.4) | 6.2 (2.7) | 21.8 (9.3) | |
CD | 68 | 115.8 (85.2) | 7.2 (5.3) | 3.2 (2.3) | 9.8 (7.2) | 0.90 |
OR (C.I.) | 0.86 (0.43–1.74) | 1.6 (0.47–5.51) | 0.91 (0.19–4.42) | 1.02 (0.40–2.61) | ||
Controls (b) | 72 | 107.8 (87.0) | 4.2 (3.3) | 3.2 (2.5) | 8.8 (7.1) | |
D1 (CC/CC) | D2 (CC/GT) | D3 (GC/CT) | D4 (CC/CT) | |||
IBD | 77 | 57.0 (74.0) | 9.9 (12.8) | NP | 6.0 (7.8) | |
OR (C.I.) | 1.17 (0.64–2.13) | 0.81 (0.37–1.76) | 1.08 (0.39–2.95) | |||
Controls (b) | 179 | 127.0 (70.9) | 27.6 (15.4) | NP | 13.0 (7.3) | |
UC | 9 | 8.0 (88.9) | 1.0 (11.0) | NP | 0.0 (0) | |
OR (C.I.) | 3.56 (0.43–29.49) | 0.65 (0.08–5.53) | — | |||
Controls (b) | 117 | 81.0 (69.2) | 18.8 (16.0) | NP | 9.0 (7.7) | |
CD | 68 | 49.0 (72.1) | 8.8 (13.0) | NP | 6.0 (8.8) | |
OR (C.I.) | 0.90 (0.41–1.95) | 0.90 (0.33–2.45) | 1.40 (0.38–5.23) | |||
Controls (b) | 72 | 46.0 (74.2) | 8.8 (14.3) | NP | 4.0 (6.5) | |
D5 (CC/GC) | D6 (CT/GT) | D7 (GT/GT) | D8 (GC/GT) | |||
IBD | 3.0 (3.9) | 1.0 (1.3) | 0.0 (0) | NP | 0.98 | |
OR (C.I.) | 0.77 (0.20–2.91) | — | — | |||
Controls | 9.0 (5.0) | 1.0 (0.6) | 1.0 (0.6) | NP | ||
UC | 0.0 (0) | 0.0 (0) | 0.0 (0) | NP | 0.67 | |
OR (C.I.) | — | — | — | |||
Controls | 6.0 (5.1) | 1.0 (0.9) | 1.0 (0.9) | NP | ||
CD | 3.0 (4.4) | 1.0 (1.5) | NP | NP | 0.98 | |
OR (C.I.) | 0.91 (0.18–4.67) | — | ||||
Controls | 3.0 (4.8) | 0.0 (0) | NP | NP |
OR: odds ratio; CI: confidence interval;
Haplotype and diplotype distribution in IBD cases with and without disease activity.
Subjects included | H1 (CC) | H2 (CT) | H3 (GC) | H4 (GT) | ||
---|---|---|---|---|---|---|
IBD | 48 | 82.9 (84.6) | 3.1 (3.2) | 2.1 (2.2) | 9.9 (10.1) | 0.83 |
OR (C.I.) | 0.99 (0.53–1.83) | 0.65 (0.19–2.21) | 0.88 (0.2–3.96) | 1.29 (0.6–2.74) | ||
Controls (b) | 191 | 323.6 (84.7) | 18.4 (4.8) | 9.4 (2.5) | 30.6 (8.0) | |
UC | 18 | 31.0 (86.0) | 1.0 (2.9) | 0.0 (0.1) | 4.0 (11.0) | 0.74 |
OR (C.I.) | 1.16 (0.42–3.18) | 0.67 (0.08–5.23) | 0.04 (0.0–749.8) | 1.3 (0.41–4.09) | ||
Controls (b) | 108 | 181.8 (84.2) | 9.2 (4.3) | 6.2 (2.9) | 18.8 (8.7) | |
CD | 31 | 51.9 (83.7) | 2.1 (3.4) | 2.1 (3.4) | 5.9 (9.5) | 0.72 |
OR (C.I.) | 0.88 (0.39–1.95) | 0.6 (0.13–2.76) | 1.79 (0.31–10.5) | 1.37 (0.49–3.86) | ||
Controls (b) | 83 | 141.8 (85.4) | 9.2 (5.5) | 3.2 (1.9) | 11.8 (7.1) | |
D1 (CC/CC) | D2 (CC/GT) | D3 (GC/CT) | D4 (CC/CT) | |||
IBD | 48 | 35.0 (71.4) | 8.9 (18.1) | NP | 2.0 (4.1) | |
OR (C.I.) | 1.04 (0.52–2.08) | 1.31 (0.57–3.01) | 0.44 (0.10–1.95) | |||
Controls (b) | 191 | 135.0 (70.7) | 27.6 (14.4) | NP | 17.0 (8.9) | |
UC | 18 | 14.0 (77.8) | 3.0 (16.4) | NP | 0.0 (0) | |
OR (C.I.) | 1.54 (0.47–5.03) | 1.07 (0.28–4.13) | — | |||
Controls (b) | 108 | 75.0 (69.4) | 16.8 (15.5) | NP | 9.0 (8.3) | |
CD | 31 | 21.0 (67.7) | 5.9 (19.0) | NP | 2.0 (6.5) | |
OR (C.I.) | 0.81 (0.33–1.97) | 1.57 (0.52–4.72) | 0.65 (0.13–3.23) | |||
Controls (b) | 83 | 60.0 (72.3) | 10.8 (13.0) | NP | 8.0 (9.6) | |
D5 (CC/GC) | D6 (CT/GT) | D7 (GT/GT) | D8 (GC/GT) | |||
IBD | 2.0 (4.1) | 1.0 (2.0) | 0.0 (0) | NP | 0.70 | |
OR (C.I.) | 0.86 (0.18–4.12) | — | — | |||
Controls | 9.0 (4.7) | 1.0 (0.5) | 1.0 (0.5) | NP | ||
UC | 0.0 (0) | 1.0 (5.6) | 0.0 (0) | NP | 0.16 | |
OR (C.I.) | — | — | — | |||
Controls | 6.0 (5.6) | 0.0 (0) | 1.0 (0.9) | NP | ||
CD | 2.0 (6.5) | 0.0 (0) | NP | NP | 0.80 | |
OR (C.I.) | 1.84 (0.29–11.57) | — | ||||
Controls | 3.0 (3.6) | 1.0 (1.2) | NP | NP |
OR: odds ratio; CI: confidence interval;
PPAR
Former studies, which investigated the impact of a polymorphic expression of PPAR
In the study presented here, we aimed at comprehensively investigating the occurring polymorphisms within the
Interestingly,
We did not find any significant association of distinct
In conclusion, we have performed a comprehensive study analyzing the role of NR1C3 genetic variants in IBD susceptibility and IBD course in a Swiss cohort of IBD patients. We showed that the polymorphic expression of the
Inflammatory bowel disease
Ulcerative colitis
Crohn’s disease
Peroxisome proliferator-activated receptor gamma
Single nucleotide polymorphism
Nuclear receptor subfamily 1, group C, member 3
Extraintestinal manifestations.
Modified truelove witts severity index
Crohn’s disease activity index.s
J. Mwinyi and C. Grete-Wenger contributed equally to this work.
The authors thank Christian Hiller for excellent technical assistance, members of our team for fruitful discussions, and the Swiss IBD Cohort Study Group (SIBDCS): Pierluigi Ballabeni, Peter Bauerfeind, Christoph Beglinger, Stefan Begré, José Bengoa, Janek Binek, Daniel Boller, Jan Borovicka, Christian Braegger, Patrick Brun, Patrick Bühr, Bernard Burnand, Rafael Camara, Dominique Criblez, Philippe de Saussure, Lukas Degen, Joakim Delarive, Tobias Ehmann, Matthias Engelmann, Ali El Wafa, Christian Felley, Alain Frei, Remus Frei, Michael Fried, Florian Froehlich, Suzanne Gallot-Lavallée, Tilman Gerlach, Martin Geyer, Marc Girardin, Oliver Goetze, Horst Haack, Serge Hediger, Peter Hengstler, Klaas Heyland, Patrick Janiak, Pascal Juillerat, Vera Kessler Brondolo, Christoph Knoblauch, Gerd A. Kullak-Ublick, Michael Manz, Rémy Meier, Christa Meyenberger, Pierre Michetti, Christian Mottet, Christoph Müller, Beat Müllhaupt, Thierry Nicolet, Andreas Nydegger, Isabelle Pache, Franziska Piccoli, Julia Pilz, Valérie Pittet, Ronald Rentsch, Jean-Pierre Rey, Silvia Rihs, Daniela Rogler, Gerhard Rogler, Markus Sagmeister, Bernhard Sauter, Niklaus Schaub, Susanne Schibli, Alain Schoepfer, Franck Seibold, Johannes Spalinger, Philippe Stadler, Michael Steuerwald, Alex Straumann, Michael Sulz, Michela Schäppi, Joël Thorens, John-Paul Vader, Stephan Vavricka, Jürg Vögtlin, Roland Von Känel, Gert Wachter, Jürg Wermuth, and Paul Wiesel. This study was financially supported by the Swiss National Science Foundation (Grant 320030_120463), the Swiss IBD Cohort Study (SNF Grant 33CSC0-108792), Zurich University Research Priority Programme “Integrative Human Physiology” (ZIHP), the Center of Clinical Research at the University Hospital Zurich, the Novartis Foundation for Biomedical Research, the IBD Research Foundation, and the Olga Mayenfisch Foundation.