OCTN1 variant L503F is associated with familial and sporadic inflammatory bowel disease.
OBJECTIVE
A two-allele haplotype of TC (OCTN1 rs1050152 and OCTN2 -207G→C) is associated with Crohn's disease (CD). The association has been replicated in different populations, but also failed in some studies. The present study is to replicate the association of OCTN1 rs1050152 and examine another variant rs272879 with familial and sporadic inflammatory bowel disease (IBD) in a cohort from central Pennsylvania, USA.


METHODS
The study samples (n=465) included 212 inflammatory bowel disease patients (CD=115, UC=97), including 103 familial (CD=55, UC=46) and 111 sporadic (CD=60, UC=51) IBD, 139 non-IBD family members from a familial IBD registry, and 114 unrelated healthy controls. A total of 12 OCTN1 variants within exonic sequences were examined. Two nonsynonymous SNPs, rs1050152 (L503F) and rs272879 (L395V) were genotyped by a PCR-based RFLP/cRFLP method and statistically analyzed. These samples with an additional 141 unrelated healthy samples were also genotyped for rs1050152 using the SNPlex™ Genotyping System.


RESULTS
The OCTN1 rs1050152 is associated with CD (OR=1.745, 95% CI=1.019-2.990, χ²=4.129, p=0.042) and with IBD (OR=1.68, 95% CI=1.052-2.676, χ²=4.732, p=0.030); while the variant rs272879 is not associated with IBD, CD or ulcerative colitis (UC). The distribution of the rs1050152 variant showed a high level of the T allele in male UC (OR=2.585, 95% CI=1.139-5.869, p=0.023) and IBD (OR=2.039, 95% CI=1.024-4.059, p=0.042) patients, and in female CD patients (OR=2.329, 95% CI=1.038-5.226, ρ value=0.039).


CONCLUSIONS
The present results replicated the association of the OCTN1 rs1050152 (L503F) variant with CD and IBD overall. A weak gender-specific effect of rs1050152 (L503F) on male UC and female CD was observed.
Department of Surgery, The Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA 17033, USA. zlin@psu.edu
Zhenwu
Z
Lin
Laurie
L
Nelson
Andre
A
Franke
Lisa
L
Poritz
Tong-Yi
TY
Li
Rongling
R
Wu
Yunhua
Y
Wang
Colin
C
MacNeill
Neal J
NJ
Thomas
Stefan
S
Schreiber
Walter A
WA
Koltun
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D004247:DNA / Q000302:isolation & purification; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D010414:Pennsylvania; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017678:Sex Distribution; D027981:Symporters; D044465:White People / Q000235:genetics; D055815:Young Adult
D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; D027981:Symporters; D004247:DNA