Association of CCK Receptor Gene Polymorphisms and Irritable Bowel Syndrome in Korean

Abstract

IntroductionCholecystokinin (CCK) belongs to a group of endogenous molecules known as brain-gut neuropeptides and functions as a neuropeptide as well as a gut hormone. It remains unclear whether genetic variation of the CCK receptor plays a role in irritable bowel syndrome (IBS). The aim of this study was to determine and compare the allele and genotype frequencies of the CCK1 receptor polymorphisms between healthy controls and patients with IBS.MethodsGenotyping of 80 patients with IBS (who met the Rome III criteria) and 76 healthy controls was performed. We performed PCR amplification for the CCK1 receptor intron 1 779 T > C and Exon 1 G > A. We confirmed polymorphisms by direct sequencing method.ResultsThere was a significantly different trend for genotypic distributions of the CCK1 receptor polymorphism between patients with IBS and healthy controls (p for trend = 0.048). The CCK1 receptor intron 1 779 T >C polymorphic type was more common in patients with 'IBS-constipation predominant (IBS-C) and IBS-mixed (IBS-M) forms' (19/31, 61.3%) than healthy controls 32/76, 42.1% adjusted odd ratio 2.43, 95% Confidence interval 1.01-5.86). The genotypic distributions of the CCK1 receptor exon 1 polymorphism were not significantly different between the two groups (p for trend = 0.223).ConclusionsCCK1 receptor polymorphisms were associated with IBS. In particular, the CCK1 receptor intron 1 779 T > C polymorphic type was associated with 'IBS-C and IBS-M'. Further studies are needed in larger number of patients with an even distribution of IBS subtypes.

Association Between SLC6A4 Serotonin Transporter Gene Lainked Polymorphic Region and ADRA2A −1291C>G and Irritable Bowel Syndrome in Korea

“…In the study which was conducted in Korea, a significant association of CCK1R intron 779 T>C polymorphism with "IBS-C and IBS-M" was reported (OR, 2.43). 13 However, in the present study, no association with IBS or subtypes was shown. It has been reported that TRPV1 945G>C polymorphism increased the expression level of mRNA and protein, in vitro.…”

“…17,18,48 Nonetheless, the genotypic distributions of most polymorphisms in controls of this study were similar to those of other studies conducted in Korea, Japan and China lending strength to the validity of our result particularly in Asian countries. 13 We also have to admit the small sample size of overall patients, especially IBS-C in this study may have limited its accuracy to detect differences between the groups. Although the proportion of IBS-C seems widely variable in Asia, 50 the recent study which was conducted in Korea based on ROME III criteria reported that the proportion of IBS-C was only 12.0%.…”

“…Therefore, the possibility of type II error cannot be excluded in each polymorphism analysis, although there were some studies which demonstrated the genetic association with modest sample size. 12,13,29 Larger studies such as multi-center studies are needed for the accurate estimation of the genotypic risk. We did not perform the correction for multiple testing in order to reduce the likelihood that real effects would be missed.…”

“…10 In addition to 5-HTTLPR polymorphism, with respect to colonic motility and sensation, the polymorphisms of G-protein β3 (GNB3) 825C>T, alpha 2A adrenergic receptor, ADRA2A −1291C>G, cholecystokinin receptor 1 (CCK1R) intron 779T>C and transient receptor potential ion channel of the vanilloid type 1 (TRPV1) 945G>C were recently investigated. [11][12][13][14][15] The genetic variation in the adrenergic receptor such as ADRA2A −1291C>G has been proposed as a mechanism for the modification of motor and sensory functions in IBS patients. 16,17 Another protein of interest is the G-protein.…”

Pathogenesis of Irritable Bowel Syndrome: Is It Really in the Gene?

“…Therapeutic blockade of CCK1 receptors (CCK1R) may stimulate gut motility and may reduce colonic transit time in patients with IBS-C. 15 A polymorphism in CCK1R gene (779T＞C) was found to be associated with slower gastric emptying among patients with IBS-C. 16 This suggests that, compared with the 779T variant, the 779C substitution results in an increased response to endogenous CCK, prolonging gastric emptying. Serotonin or 5-hydroxytryptamine (5-HT) is an important molecule for stimulating GI motility, secretion and enhancing visceral sensation.…”