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

Abstract：

BACKGROUND/AIMS:Despite numerous studies on the relation of genetic polymorphisms with irritable bowel syndrome (IBS), the results still remain inconclusive. The aim of this study was to assess the possible association between SLC6A4 serotonin transporter gene linked polymorphic region (5-HTTLPR), ADRA2A -1291C>G, GNB3 825C>T, CCK1R intron 779T>C and TRPV1 945G>C polymorphisms and IBS based on Rome III criteria in Korea. METHODS:Study subjects were prospectively recruited from visitors to Seoul National University Bundang Hospital between July 2009 and January 2014. Ninety-nine IBS patients and 171 healthy controls were enrolled. Polymorphisms of above-mentioned 5 genes were genotyped. Serum serotonin from 101 participants was measured by ELISA and compared according to SLC6A4 5-HTTLPR polymorphisms and IBS subtypes. RESULTS:Regarding SLC6A4 5-HTTLPR polymorphism, L/L genotype was significantly associated with the total IBS, constipation predominant IBS (IBS-C) and mixture of diarrhea and constipation IBS (IBS-M) (adjusted OR: 4.35, 95% CI: 1.04-16.67; adjusted OR: 11.11, 95% CI: 1.69-50.00 and adjusted OR: 5.56, 95% CI: 1.05-33.33, respectively). Carrying ADRA2A -1291G allele was significantly associated with total IBS and diarrhea predominant IBS (adjusted OR: 3.37, 95% CI: 1.16-9.77 and adjusted OR: 5.64, 95% CI: 1.18-27.01, respectively). IBS-C patients showed reduced level of serum serotonin compared to controls and patients with diarrhea predominant IBS (50.2 ng/mL vs. 69.0 ng/mL and 92.9 ng/mL, P = 0.017 and P = 0.001, respectively). CONCLUSIONS:Genetic polymorphisms of SLC6A4 5-HTTLPR and ADRA2A -1291C>G could be one of the pathophysiological factors of IBS in Korea. Reduced serum serotonin shown in the IBS-C group suggested a role of serotonin in IBS, but large study is needed for confirming genotypic difference in serum serotonin level.

journal_name

J Neurogastroenterol Motil

journal_title

Journal of neurogastroenterology and motility

authors

Choi YJ,Hwang SW,Kim N,Park JH,Oh JC,Lee DH

doi

10.5056/jnm14020

subject

Has Abstract

pub_date

2014-07-31 00:00:00

pages

388-99

issue

eissn

2093-0879

issn

2093-0887

pii

jnm14020

journal_volume

pub_type

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