Introduction 2003 2005 + 2002 HLA-DQA DQB 2005 2004 2004 2004 2001 SPINK SPINK1 SPINK2 SPINK4 SPINK5 SPINK SPINK1 SPINK5 SPINK SPINK5L2 SPINK6 SPINK5L3 SPINK7 SPINK9 SPINK SPINK5 SPINK SPINK1 2001 SPINK2 2004 SPINK4 1989 1992 2003 SPINK5 1999 SPINK5 2002 SPINK5 2005 2005 SPINK5 2005 SPINK1 SPINK5 2003 2005 SPINK4 2004 SPINK SPINK1 SPINK4 SPINK5 SPINK Materials and methods Patient material 2001 1 n n n SPINK SPINK4 SPINK4 P SPINK4 2004 SPINK4 SPINK4 Fig. 1 SPINK NC MIII MII M0 MIII MIII MII MIII MII MI M0 SPINK1 a SPINK2 b SPINK4 c SPINK5 d e SPINK SPINK2 GUSB Error bars Expression study 2004 SPINK1 SPINK2 SPINK4 SPINK5 Genetic association and data analysis SPINK1 SPINK2 SPINK4 SPINK5 2005 SPINK 1 2 P χ 2 Table 1 SPINK   n n     Allele Allele counts Allele frequency (%) Allele counts Allele frequency (%) Gene name SNP i.d. Position* Minor/major Minor Major Minor Major Minor Major Minor Major χ 2 P SPINK1 rs10515593 147,178,993 A/G 119 449 21 79 76 268 22.1 77.9 0.166 0.6834 SPINK1 rs3777125 147,184,010 C/G 228 336 40.4 59.6 150 200 42.9 57.1 0.527 0.4681 SPINK1 rs4705204 147,195,313 C/A 125 429 22.6 77.4 60 276 17.9 82.1 2.813 0.0935 SPINK1 rs891992 147,205,707 G/A 77 483 13.8 86.2 47 303 13.4 86.6 0.019 0.8906 SPINK2 rs10015630 57,520,070 A/G 216 328 39.7 60.3 136 216 38.6 61.4 0.102 0.7489 SPINK2 rs781542 57,528,232 G/A 220 390 36.1 63.9 123 221 35.8 64.2 0.009 0.9237 SPINK4 rs563353 33,206,428 G/C 120 472 20.3 79.7 67 279 19.4 80.6 0.112 0.7375 SPINK4 rs563512 33,206,484 G/A 50 556 8.3 91.7 36 310 10.4 89.6 1.243 0.2648 SPINK4 rs891671 33,222,271 G/T 70 540 11.5 88.5 52 304 14.6 85.4 1.998 0.1575 SPINK4 rs706107** 33,230,225 A/G 117 499 19 81 81 269 23.1 76.9 2.358 0.1246 SPINK4 rs706109 33,230,668 A/G 118 486 19.5 80.5 82 276 22.9 77.1 1.549 0.2133 SPINK4 rs706115 33,243,605 G/C 77 537 12.5 87.5 52 308 14.4 85.6 0.716 0.3975 SPINK5 rs3756688 147,422,972 G/A 232 380 37.9 62.1 135 221 37.9 62.1 0.000 0.9968 SPINK5 rs4472254 147,433,830 A/C 240 376 39 61 142 214 39.9 60.1 0.081 0.7757 SPINK5 rs4519913 147,452,004 G/A 279 331 45.7 54.3 168 192 46.7 53.3 0.079 0.7792 SPINK5 rs1422987 147,466,552 T/C 49 559 8.1 91.9 27 329 7.6 92.4 0.070 0.7917 SPINK5 rs3815740 147,471,386 G/A 38 574 6.2 93.8 21 337 5.9 94.1 0.047 0.8291 SPINK5 rs2052532 147,476,500 G/A 200 414 32.6 67.4 117 241 32.7 67.3 0.001 0.9723 SPINK5 rs3764930 147,485,309 G/A 199 413 32.5 67.5 117 243 32.5 67.5 0.000 0.9958 *Basepair position according to NCBI build 35.1 **Coding SNP, nonsynonymous change (Val7Ile) Fig. 2 SPINK upper horizontal line vertical bars numbered asterisks 1 SPINK4 4 arrow points lower portion D Darker red D numbers D DNA sequence analysis SPINK4 3 SPINK4 1 Fig. 3 SPINK4 boxed shaded top to bottom 1 1 2 3 4 02 08 21 31 32 41 bold Results SPINK SPINK 1 SPINK4 1 SPINK4 SPINK4 1 SPINK SPINK SPINK1 SPINK4 SPINK2 SPINK5 SPINK2 1 SPINK4 SPINK4 SPINK SPINK SPINK1 2 4 5 SPINK 2 1 SPINK4 1992 2004 SPINK4 P P 2 SPINK Table 2 SPINK4   n n     Allele Allele counts Allele frequency (%) Allele counts Allele frequency (%) Gene name SNP i.d. Position* Minor/major Minor Major Minor Major Minor Major Minor Major χ 2 P SPINK4 rs891671 33,222,271 G/T 126 814 13.4 86.6 158 904 14.9 85.1 0.889 0.3457 SPINK4 rs706107** 33,230,225 A/G 205 737 21.8 78.2 242 814 22.9 77.1 0.382 0.5365 SPINK4 rs706109 33,230,668 A/G 212 724 22.6 77.4 242 816 22.9 77.1 0.014 0.9053 *Basepair position according to NCBI build 35.1 **Coding SNP, nonsynonymous change (Val7Ile) SPINK4 3 2004 SPINK4 SPINK4 3 SPINK4 SPINK4 3 SPINK4 Discussion 2004 2004 2005 2005 2005 MYO9B 2005 2005 2004 2005 SPINK SPINK4 SPINK4 SPINK4 SPINK4 SPINK SPINK SPINK1 2 5 SPINK4 SPINK4 SPINK4 SPINK SPINK4 SPINK 2003 1998 2003 CARD15 NOD2 2002 2003 SPINK5 2005 2005 SPINK SPINK5L2 SPINK6 SPINK5L3 SPINK7 SPINK9 SPINK1 SPINK5 Electronic Supplementary Material Below is the link to the electronic supplementary material. Supplementary Fig. S1 (GIF 14.0 kb) Supplementary Table 1 SPINK4