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 |
Initially 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;
Minor allele frequency (MAF) according to SNP data from the HapMap CEPH collection;
TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA, United States);
With 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);
Linkage 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.