5-HTTLPR and STin2 polymorphisms in the serotonin transporter gene and irritable bowel syndrome: effect of bowel habit and sex.
BACKGROUND
Conflicting data exist on the association between functional polymorphisms in the serotonin reuptake transporter (SERT) gene (SLC6A4) and irritable bowel syndrome (IBS). This may be partly because of small participant numbers and varying ethnic origin and sex within the cohorts studied.


OBJECTIVE
To reassess the potential association between the SERT polymorphisms 5-HTTLPR and STin2 in both male and female IBS patients with diarrhoea (IBS-D) and constipation (IBS-C) compared with healthy volunteers.


METHODS
In this case-control study, 196 Caucasian Rome II IBS patients [97 IBS-D (aged 18-66 years; 67 female) and 99 IBS-C (aged 18-65 years; 95 female)] and 92 Caucasian healthy volunteers (aged 18-63 years; 60 female) from the UK had genomic DNA extracted from peripheral blood and the 5-HTTLPR and STin2 polymorphisms genotyped.


RESULTS
The frequency of the 5-HTTLPR (ss) genotype was slightly lower in both IBS-D (16.5%) and IBS-C (14.3%) patients compared with controls (23.9%), although not significantly (P<or=0.191). This seemed to be related to a reduction in the frequency of the 5-HTTLPR (ss) genotype in male patients, particularly those with IBS-D [IBS-D 10%, IBS-C 25%, controls 37.5%; P=0.01 for IBS-D vs. controls; odds ratio (95% confidence interval) for 5-HTTLPR (ss) vs. 5-HTTLPR (non-ss)=0.185 (0.046-0.744)] than in female patients (IBS-D 19.4%, IBS-C 13.8%, controls 16.7%). There were no differences in the frequencies of either the 5-HTTLPR (ll) or (ls), or STin2 genotypes between any of the three groups.


CONCLUSIONS
Our finding that male IBS-D patients have a reduced frequency of the 5-HTTLPR (ss) genotype contradicts three earlier studies of a similar size, which did not take sex into account. Therefore, replication studies in even larger cohorts, stratifying for sex and endophenotypes, after assessing physiological and psychological traits, are required to unravel the contribution of SERT polymorphisms to the IBS phenotype.
Niesler
Beate
B
Department of Human Molecular Genetics, University of Heidelberg, Heidelberg, Germany.
Kapeller
Johannes
J
Fell
Catherine
C
Atkinson
Wendy
W
Möller
Dorothee
D
Fischer
Christine
C
Whorwell
Peter
P
Houghton
Lesley A
LA
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003248:Constipation / Q000235:genetics; D003967:Diarrhea / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012737:Sex Factors; D055815:Young Adult
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins