Expression and functional analysis of intestinal organic cation/L-carnitine transporter (OCTN) in Crohn's disease.
BACKGROUND
The IBD5 locus is a genetic risk factor for IBD, particularly Crohn's Disease, coding for the organic cation/carnitine transporters (OCTN1 and 2). Two variants of OCTN are associated with susceptibility to Crohn's Disease. Modified transport of carnitine in vitro has been reported for a polymorphism of OCTN1. The aim was to investigate the function of intestinal OCTNs in IBD in relation to genetic polymorphisms.


METHODS
Intestinal tissue was obtained from endoscopic biopsies and surgical resections from IBD patients (n=33 and 14, resp.) and controls (n=22 and 14, resp.). OCTN protein levels were measured in intestinal biopsies and carnitine transport was quantified in intestinal resections.


RESULTS
OCTN1 protein levels were significantly higher in ileal versus colonic tissue (2.95% ± 0.4 vs 0.66% ± 0.2, resp.; p<0.0002). OCTN1 expression was higher in Crohn's disease patients with mutant homozygous or heterozygous genotypes (0.6% ± 0.1 vs 3% ± 0.8, resp., p<0.02). Carnitine transport was very rapid and Na+ dependent (10s). It was not different comparing Crohn's Disease and control groups (0.45 ± 0.12 vs 0.51 ± 0.12 nM carnitine/mg prot/min, resp.). Carnitine transport tended to be higher in subjects with mutant homozygous and heterozygous OCTN1 and OCTN2 genotypes (0.19 vs 0.59 and 0.25 vs 0.6, respectively).


CONCLUSIONS
The present data reveal that OCTN protein levels appear to be similar in intestinal tissue from Crohn's Disease patients and controls. Overall, ileal carnitine transport appears to as well equal in Crohn's Disease and control groups. However, there was a trend towards higher carnitine transport in subjects with OCTN1 and OCTN2 mutations.
DigestiveLab, Research Institute, McGill University Health Centre, Montreal, QC, Canada. marcgirardin@gmail.com
Marc
M
Girardin
Serge
S
Dionne
Philippe
P
Goyette
John
J
Rioux
Alain
A
Bitton
Ihsan
I
Elimrani
Patrick
P
Charlebois
Ijaz
I
Qureshi
Emile
E
Levy
Ernest G
EG
Seidman
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D002331:Carnitine / Q000493:pharmacokinetics*; D002648:Child; D003093:Colitis, Ulcerative / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007082:Ileum / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D012964:Sodium / Q000494:pharmacology; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D055815:Young Adult
D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D012964:Sodium; D002331:Carnitine