Table 3.
Candidate Gene Studies in IBS
| Protein (gene) | Polymorphism | Reference | Case sample size | Finding summary |
|---|---|---|---|---|
| Serotonin pathway | ||||
| Serotonin transporter (SLC6A4) | 5-HTT LPR | Pata et al, Am J Gastroenterol 200254 | 54 | No association; LS associated with IBS-D |
| Kim et al, Gut 200455 | 256 | No association | ||
| Yeo et al, Gut 200456 | 186 | Only patients with IBS-D; SS associated with IBS-D | ||
| Lee et al, Korean J Gastroenterol 200457 | 33 | No association | ||
| Park et al, Neurogastroenterol Motil 200658 | 190 | |||
| Saito et al, Neurogastroenterol Motil 200759 | 50 | No association; S associated with IBS with a mixed bowel pattern | ||
| Li et al, Dig Dis Sci 200760 | 87 | No association; LL associated with IBS-C | ||
| Sikander et al, J Clin Gastroenterol 200961 | 151 | No association; SS associated with IBS-C | ||
| Niesler et al, Eur J Gastroenterol Hepatol 200962 | 196 | N/A; no association with IBS-C or IBS-D; lower frequency of SS in male IBS-D | ||
| Kohn et al, Dig Dis Sci 200963 | 186 | No association with IBS | ||
| Saito et al, Gastroenterology 200964 | 312 | No association with IBS or IBS subtypes | ||
| STin2 VNTR | Pata et al, Am J Gastroenterol 200254 | 54 | No association with IBS or IBS subtypes | |
| Niesler et al, Eur J Gastroenterol Hepatol 200962 | 196 | No overall IBS analysis performed; no association with IBS-C or IBS-D | ||
| Kohn et al, Dig Dis Sci 200963 | 186 | No association | ||
| rs25531 | Kohn et al, Dig Dis Sci 200963 | 186 | G allele associated with IBS | |
| 5-HT2A receptor subunit (HTR2A) | 102T>C | Pata et al, J Clin Gastroenterol 200465 | 54 | No association |
| −1438G>A | Pata et al, J Clin Gastroenterol 200465 | 54 | No association | |
| 5-HT3A receptor Type A subunit (HT3A) | −42C>T | Kapeller et al, Hum Mol Genet 200866 | 200 | No overall IBS analysis performed; no association with IBS-C; C/T genotype increased frequency in UK IBS-D, not replicated in another cohort |
| −25C>T | Kapeller et al, Hum Mol Genet 200866 | 200 | No overall IBS analysis performed; no association with IBS-D or IBS-C | |
| *70C>T | Kapeller et al, Hum Mol Genet 200866 | 200 | No overall IBS analysis performed; no association with IBS-D or IBS-C | |
| *503C>T | Kapeller et al, Hum Mol Genet 200866 | 200 | No overall IBS analysis performed; no association with IBS-D or IBS-C | |
| 5-HT3B receptor Type B subunit | 386A>C | Fukudo et al, Neuroimage 200925 | 28 | AC and CC subjects had differential brain activation compared with AA subjects |
| 5-HT3E receptor Type E subunit (HT3E) | *76G>A | Kapeller et al, Hum Mol Genet 200866 | 200 | No overall IBS analysis performed; G/A genotype more common in IBS-D (odds ratio, 8.53; P <.05), replicated in separate cohort |
| 5-HT3C receptor Type C subunit (5-HT3C) | 489C>A | Kapeller et al, Gastroenterology 200967 | 197 | CC associated with female patients with IBS-D |
| *115T>G | Kapeller et al, Hum Mol Genet 200866 | 200 | No overall IBS analysis performed; no association with IBS-D or IBS-C | |
| *138C>T | Kapeller et al, Hum Mol Genet 200866 | 200 | No overall IBS analysis performed; no association with IBS-D or IBS-C | |
| −189G>A | Kapeller et al, Hum Mol Genet 200866 | 200 | No overall IBS analysis performed; no association with IBS-D or IBS-C | |
| Inflammatory markers | ||||
| Interleukin-10 | −1082G>A | Gonsalkorale et al, Gut 200368 | 230 | AA or GA associated |
| Van der Veek et al, Gastroenterology 200469 | 111 | No association | ||
| −819C>T | Van der Veek et al, Gastroenterology 200469 | 111 | No association | |
| Transforming growth factor β1 | +869 T>C | Gonsalkorale et al, Gut 200368 | 230 | No association |
| +915G>C | Gonsalkorale et al, Gut 200368 | 230 | No association | |
| Tumor necrosis factor α | −308G>A | Van der Veek et al, Gastroenterology 200469 | 111 | GA associated |
| Adrenergic pathway | ||||
| Norepinephrine transporter (NET) | 237G>C | Kim et al, Gut 200455 | 276 | Not detected |
| α2A-adrenergic receptor (A2AR) | 753C>G | Kim et al, Gut 200455 | 276 | Not detected |
| 1291C>G | Kim et al, Gut 200455 | 276 | Borderline association with IBS-C | |
| Sikander et al, Clin Chim Acta 200970 | 151 | Not associated with IBS overall; non-CC genotype associated with IBS-D | ||
| Alphaα2C-adrenergic receptor (A2CR) | Del 332-335 | Kim et al, Gut 200455 | ||
| Other | ||||
| β3 subunit G protein (GNβ3) | 825C>T | Holtmann et al, Gastroenterology 200471 | 20 | No association |
| Andresen et al, Gastroenterology 200672 | 233 | No association | ||
| Saito et al, Neurogastroenterol Motil 200759 | 50 | No association | ||
| Saito et al, Gastroenterology 200964 | 312 | No association with IBS overall, but there was a gene-environment interaction between this SNP and prior gastrointestinal infection with IBS | ||
| Cholecystokinin type 1 receptor (CCK1-R) | 266G>C 8641G>A 984T>C |
Colucci et al, Gastroenterology 200973 | 60 | No association between these 3 SNPs with IBS or IBS symptom severity |
| Nav1.5 channel (SCN5A) | G298S | Saito et al, Am J Physiol Gastrointest Liver Physiol 200974 | 49 | Reported in 1 patient with IBS-D |
| 43 genes (inflammatory, intestinal barrier, serotonin) | 78 SNPs | Villani et al, Gastroenterology 200975 | SNPs in CDH1, TLR9, and IL6 were associated with postinfectious IBS | |
| 43 genes (inflammatory, intestinal barrier, serotonin) | 78 SNPs | Villani et al, Gastroenterology 200975 | SNPs in IL10 and HTR2A associated with IBS-D in female patients; SNPs in CDH1, TLR9, IL6 were not associated with non–postinfectious IBS | |
IBS-C, constipation-predominant irritable bowel syndrome.