Extended Data Table 3.
Genotype analysis for human TIM3 alleles in Inflammatory bowel disease
| a. Study numbers | ||
|---|---|---|
| Source | Number of individuals |
Genoytpe distribution |
| German IBD patients | 5,598 | AA=3/AG=77/GG=5,518 |
| German CD patients | 3,975 | AA=2/AG=54/GG=3,919 |
| German UC patients | 1,623 | AA=1/AG=23/GG=1,599 |
| German healthy controls | 3,928 | AA=0/AG=50/GG=3,878 |
| EVS, European Americans | 4,300 | AA=0/AG=36/GG=4,264 |
| b. Studied TIM3 SNPs | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CD patients | UC patients | IBD patients | Healthy controls | |||||||||
| rs-number | AA | AB | BB | AA | AB | BB | AA | AB | BB | AA | AB | BB |
| rs201054625 | 2329 | 0 | 0 | 1448 | 0 | 0 | 3777 | 0 | 0 | 2913 | 0 | 0 |
| rs145478313 | 2302 | 2 | 0 | 1445 | 0 | 0 | 3747 | 2 | 0 | 2875 | 3 | 0 |
| rs190484372 | 2318 | 0 | 0 | 1439 | 0 | 0 | 3757 | 0 | 0 | 2894 | 0 | 0 |
| rs147827860 | 2284 | 42 | 2 | 1423 | 22 | 1 | 3707 | 64 | 3 | 2879 | 32 | 0 |
| rs35960726 | 2305 | 24 | 0 | 1425 | 22 | 0 | 3730 | 46 | 0 | 2861 | 51 | 0 |
| rs181855375 | 2308 | 0 | 0 | 1442 | 0 | 0 | 3750 | 0 | 0 | 2896 | 0 | 0 |
| rs184868814 | 2328 | 1 | 0 | 1447 | 0 | 0 | 3775 | 1 | 0 | 2912 | 1 | 0 |
| rs201750016 | 2275 | 0 | 0 | 1433 | 0 | 0 | 3708 | 0 | 0 | 2839 | 0 | 0 |
| rs41283181 | 2314 | 1 | 0 | 1444 | 0 | 0 | 3758 | 1 | 0 | 2894 | 0 | 0 |
| rs147605860 | 2329 | 0 | 0 | 1447 | 0 | 0 | 3776 | 0 | 0 | 2913 | 0 | 0 |
| rs142180056 | 2329 | 0 | 0 | 1448 | 0 | 0 | 3777 | 0 | 0 | 2913 | 0 | 0 |
| c. Clinical data | |||
|---|---|---|---|
| Clinical information | Patient |
||
| 1 | 2 | 3 | |
| Diagnosis | CD | CD | UC |
| Sex | male | female | male |
| Age of onset | 33 | 13 | 40 |
| Disease localisation | Colon | Ileum, colon, rectum | Colon |
| Disease characteristics | Entero-cutaneous fistula and colonic stenosis | Snail-track ulcers, anal stenosis, granulomas, perianal abscesses and fistulas | Perianal fistula |
| Extraintestinal manifestations | Pancreatitis | Eye, joints, skin | Skin |
| Treatment | Azathioprine, ASA, steroids | Azathioprine, corticosteroids | unknown |
| Surgery | Colostomy at age 44, two large bowel surgeries in the following 3 years | Surgery at ages 19 and 21 | unknown |
| Other | Iron and selenium deficincy, hyperuricemia, depression | Chronic active CD, refractory to immunosuppression, hypertension | Family history of IBD |
Genotype distribution for 11 TIM3 variants in CD, UC and IBD patients and healthy controls. A specifies the major, B the minor allele.
a, Number of successfully genotyped German patients and controls and corresponding distribution of genotypes for the Thr101Ile missense variant in TIM3, including the genotype distribution in individuals of European descent (European Americans) downloaded from the Exome Variant Server (EVS), NHLBI GO Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). Genotyping 11 rare variants in TIM3, in a cohort of 5,634 inflammatory bowel disease and 3,940 control subjects, we observed homozygous rs147827860 (Thr101Ile) carriage exclusively in three IBD subjects (2 Crohn’s disease (CD) and 1 ulcerative colitis (UC)), but no control subjects which significantly deviated from Hardy–Weinberg equilibrium in IBD cases (P = 0.0033) but not controls (P = 1.00). b, Description of TIM3 single nucleotide polymorphisms (SNPs) analysed in cohorts described in a. c, Clinical data for the three patients found to be homozygous for the rs147827860 (Thr101Ile) variant.