Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease

Table 2 Single nucleotide polymorphism markers in the genetic regions of Claudin-1, Claudin-2 and Claudin-4

Candidate gene	SNP rs number1	MAF2	Assay ID3	Position in kbp relative candidate gene and location4	Coverage5
CLDN1	rs1491991	0.25	C_7550365_10	-66.3 (5’-flanking region)	CLDN16
	rs3732923	0.41	C_27509271_10	5.5 (intron 1)	CLDN1 (from promoter until first two thirds of intron 1)
	rs3732924	0.29	C_8528578_10	5.6 (intron 1)	CLDN1 (from promoter until first two thirds of intron 1)
	rs9848283	0.49	C_2057729_10	6.4 (intron 1)	CLDN1 (from promoter until first two thirds of intron 1)
	rs12629166	0.47	C_2057718_10	13.8 (intron 3)	CLDN1 (from second intron until 3’-flanking region)
	rs7620166	0.41	C_8528273_10	45.9 (3’-flanking region)	CLDN1 (from second intron until 3’-flanking region)
	rs567408	0.42	C_1587588_10	94.5 (3’-flanking region)	intergenic block
	rs536435	0.42	C_1587674_10	155.3 (3’-flanking region)	LOC391603
CLDN2	rs4409525	0.34	C_382795_10	-23.3 (5’-flanking region)	RIPPLY1, TBC1D8B
	rs5917027	0.48	C_11771710_10	-1.0 (5’-flanking region)	CLDN2, MORC4
	rs12014762	0.21	C_2013132_20	20.0 (3’-flanking region)	CLDN2, MORC4
CLDN4	rs4131376	0.43	C_26657639_10	-56.9 (5’-flanking region)	ABHD11, CLDN3, CLDN4, WBSCR27, WBSCR28
	rs8629	0.18	C_7493975_10	0.3 (exon 1)	ABHD11, CLDN3, CLDN4, WBSCR27, WBSCR28

¹Initially all of the selected single nucleotide polymorphism (SNP) markers were evaluated, using the Hapolview software 4.0[52], for linkage disequilibrium (LD) and association to inflammatory bowel disease (IBD) in a case-control study using a subset of Swedish IBD patients (73, 39 and 42 individuals with IBD, Crohn’s disease (CD) or ulcerative colitis, respectively). Because of significant associations to CD, SNP markers for claudin (CLDN)1 (rs7620166) and CLDN2 (rs12014762) were chosen for further evaluation on the complete case-control. Even though non of the CLDN4 SNP markers showed evidence of association to any of the disease categories rs8629 was included for further evaluation;

²Minor allele frequency (MAF) according to SNP data from the HapMap CEPH collection;

³TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA, United States);

⁴With respect to each candidate gene, SNP positions are defined relative a genomic reference sequence. The first nucleotide of a reference cDNA sequence has been designated +1, with the preceeding genomic position being -1. The following reference sequences have been used for CLDN1 NT_005612.15 (genomic) and NM_021101.3 (mRNA), CLDN2 NT_011651.16 (genomic) and NM_020384.2 (mRNA) and CLDN4 NT_007758.11 (genomic) and NM_001305.3 (mRNA);

⁵Linkage blocks have been defined using SNP data from the HapMap CEPH collection and the SNP browser software with 0.3 LDU (linkage disequilibrium units) as threshold for linkage block computation.