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char = r;code = 114
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char = i;code = 105
char = c;code = 99
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char = e;code = 101
char = a;code = 97
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char = i;code = 105
char = t;code = 116
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char = s;code = 115
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char = ;code = 32
char = d;code = 100
char = e;code = 101
char = c;code = 99
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char = i;code = 105
char = n;code = 110
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char = h;code = 104
char = e;code = 101
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char = r;code = 114
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = -;code = 45
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = k;code = 107
char = ;code = 32
char = S;code = 83
char = P;code = 80
char = I;code = 73
char = N;code = 78
char = K;code = 75
char = 1;code = 49
char = ;code = 32
char = N;code = 78
char = 3;code = 51
char = 4;code = 52
char = S;code = 83
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char = h;code = 104
char = a;code = 97
char = p;code = 112
char = l;code = 108
char = o;code = 111
char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = m;code = 109
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char = t;code = 116
char = a;code = 97
char = -;code = 45
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
result sql = Pathways to injury in chronic pancreatitis: decoding the role of the high-risk SPINK1 N34S haplotype using meta-analysis.
Pathways to injury in chronic pancreatitis: decoding the role of the high-risk SPINK1 N34S haplotype using meta-analysis.
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char = ;code = 32
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char = o;code = 111
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char = K;code = 75
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char = t;code = 116
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char = W;code = 87
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char = ;code = 32
char = C;code = 67
char = P;code = 80
char = ;code = 32
char = (;code = 40
char = 2;code = 50
char = ,;code = 44
char = 4;code = 52
char = 2;code = 50
char = 1;code = 49
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = 4;code = 52
char = ,;code = 44
char = 8;code = 56
char = 5;code = 53
char = 7;code = 55
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = s;code = 115
char = );code = 41
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = -;code = 45
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = S;code = 83
char = P;code = 80
char = I;code = 73
char = N;code = 78
char = K;code = 75
char = 1;code = 49
char = ;code = 32
char = N;code = 78
char = 3;code = 51
char = 4;code = 52
char = S;code = 83
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = o;code = 111
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = -;code = 45
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = o;code = 111
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = U;code = 85
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = -;code = 45
char = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = y;code = 121
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = -;code = 45
char = c;code = 99
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = u;code = 117
char = r;code = 114
char = ;code = 32
char = 2;code = 50
char = 4;code = 52
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = u;code = 117
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = S;code = 83
char = P;code = 80
char = I;code = 73
char = N;code = 78
char = K;code = 75
char = 1;code = 49
char = ;code = 32
char = N;code = 78
char = 3;code = 51
char = 4;code = 52
char = S;code = 83
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = g;code = 103
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = C;code = 67
char = P;code = 80
char = ;code = 32
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = (;code = 40
char = O;code = 79
char = R;code = 82
char = ;code = 32
char = 1;code = 49
char = 1;code = 49
char = .;code = 46
char = 0;code = 48
char = 0;code = 48
char = ;;code = 59
char = ;code = 32
char = 9;code = 57
char = 5;code = 53
char = %;code = 37
char = ;code = 32
char = C;code = 67
char = I;code = 73
char = :;code = 58
char = ;code = 32
char = 7;code = 55
char = .;code = 46
char = 5;code = 53
char = 9;code = 57
char = -;code = 45
char = 1;code = 49
char = 5;code = 53
char = .;code = 46
char = 9;code = 57
char = 3;code = 51
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = S;code = 83
char = P;code = 80
char = I;code = 73
char = N;code = 78
char = K;code = 75
char = 1;code = 49
char = ;code = 32
char = N;code = 78
char = 3;code = 51
char = 4;code = 52
char = S;code = 83
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = o;code = 111
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = C;code = 67
char = P;code = 80
char = ;code = 32
char = (;code = 40
char = O;code = 79
char = R;code = 82
char = ;code = 32
char = 4;code = 52
char = .;code = 46
char = 9;code = 57
char = 8;code = 56
char = ,;code = 44
char = ;code = 32
char = 9;code = 57
char = 5;code = 53
char = %;code = 37
char = ;code = 32
char = C;code = 67
char = I;code = 73
char = :;code = 58
char = ;code = 32
char = 3;code = 51
char = .;code = 46
char = 1;code = 49
char = 6;code = 54
char = -;code = 45
char = 7;code = 55
char = .;code = 46
char = 8;code = 56
char = 5;code = 53
char = );code = 41
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = C;code = 67
char = P;code = 80
char = ;code = 32
char = (;code = 40
char = O;code = 79
char = R;code = 82
char = ;code = 32
char = 1;code = 49
char = 4;code = 52
char = .;code = 46
char = 9;code = 57
char = 7;code = 55
char = ,;code = 44
char = ;code = 32
char = 9;code = 57
char = 5;code = 53
char = %;code = 37
char = ;code = 32
char = C;code = 67
char = .;code = 46
char = I;code = 73
char = .;code = 46
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 9;code = 57
char = .;code = 46
char = 0;code = 48
char = 9;code = 57
char = -;code = 45
char = 2;code = 50
char = 4;code = 52
char = .;code = 46
char = 6;code = 54
char = 7;code = 55
char = );code = 41
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = C;code = 67
char = P;code = 80
char = ;code = 32
char = (;code = 40
char = O;code = 79
char = R;code = 82
char = ;code = 32
char = 1;code = 49
char = 9;code = 57
char = .;code = 46
char = 1;code = 49
char = 5;code = 53
char = ,;code = 44
char = ;code = 32
char = 9;code = 57
char = 5;code = 53
char = %;code = 37
char = ;code = 32
char = C;code = 67
char = .;code = 46
char = I;code = 73
char = .;code = 46
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 8;code = 56
char = .;code = 46
char = 8;code = 56
char = 3;code = 51
char = -;code = 45
char = 4;code = 52
char = 1;code = 49
char = .;code = 46
char = 5;code = 53
char = 6;code = 54
char = );code = 41
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = z;code = 122
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = C;code = 67
char = P;code = 80
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = x;code = 120
char = ;code = 32
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = y;code = 121
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = I;code = 73
char = (;code = 40
char = 2;code = 50
char = );code = 41
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 8;code = 56
char = 0;code = 48
char = .;code = 46
char = 9;code = 57
char = 5;code = 53
char = %;code = 37
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = S;code = 83
char = P;code = 80
char = I;code = 73
char = N;code = 78
char = K;code = 75
char = 1;code = 49
char = ;code = 32
char = N;code = 78
char = 3;code = 51
char = 4;code = 52
char = S;code = 83
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = o;code = 111
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = j;code = 106
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = C;code = 67
char = P;code = 80
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = y;code = 121
char = p;code = 112
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = p;code = 112
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result sql = BACKGROUND : The complex interactions between recurrent trypsin-mediated pancreatic injury, alcohol-associated pancreatic injury and SPINK1 polymorphisms in chronic pancreatitis (CP) are undefined. We hypothesize that CP occurs as a result of multiple pathological mechanisms (pathways) that are initiated by different metabolic or environmental factors (etiologies) and may be influenced differentially by downstream genetic risk factors. We tested this hypothesis by evaluating the differences in effect size of the high risk SPINK1 N34S haplotype on CP from multiple etiologies after combining clinical reports of SPINK1 N34S frequency using meta-analysis.

METHODS AND FINDINGS : The Pubmed and the Embase databases were reviewed. We studied 24 reports of SPINK1 N34S in CP (2,421 cases, 4,857 controls) using reported etiological factors as surrogates for pathways and multiple meta-analyses to determine the differential effects of SPINK1 N34S between alcoholic and non-alcoholic etiologies. Using estimates of between-study heterogeneity, we sub-classified our 24 studies into four specific clusters. We found that SPINK1 N34S is strongly associated with CP overall (OR 11.00; 95% CI: 7.59-15.93), but the effect of SPINK1 N34S in alcoholic CP (OR 4.98, 95% CI: 3.16-7.85) was significantly smaller than in idiopathic CP (OR 14.97, 95% C.I. = 9.09-24.67) or tropical CP (OR 19.15, 95% C.I. = 8.83-41.56). Studies analyzing familial CP showed very high heterogeneity suggestive of a complex etiology with an I(2) = 80.95%.

CONCLUSION : The small effect of SPINK1 N34S in alcoholic subjects suggests that CP is driven through a different pathway that is largely trypsin-independent. The results also suggest that large effect sizes of SPINK1 N34S in small candidate gene studies in CP may be related to a mixture of multiple etiologic pathways leading to the same clinical endpoint.

Publication: PLoS ONE 2008 ;3(4)::e2003. :doi: 10.1371/journal.pone.0002003.
Publication Date: 2008
Study Author(s): Aoun, Elie;Chang, Chung-Chou H;Greer, Julia B;Papachristou, Georgios I;Barmada, M Michael;Whitcomb, David C;
Institution: Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Shortcut link to this study:
BACKGROUND : The complex interactions between recurrent trypsin-mediated pancreatic injury, alcohol-associated pancreatic injury and SPINK1 polymorphisms in chronic pancreatitis (CP) are undefined. We hypothesize that CP occurs as a result of multiple pathological mechanisms (pathways) that are initiated by different metabolic or environmental factors (etiologies) and may be influenced differentially by downstream genetic risk factors. We tested this hypothesis by evaluating the differences in effect size of the high risk SPINK1 N34S haplotype on CP from multiple etiologies after combining clinical reports of SPINK1 N34S frequency using meta-analysis.

METHODS AND FINDINGS : The Pubmed and the Embase databases were reviewed. We studied 24 reports of SPINK1 N34S in CP (2,421 cases, 4,857 controls) using reported etiological factors as surrogates for pathways and multiple meta-analyses to determine the differential effects of SPINK1 N34S between alcoholic and non-alcoholic etiologies. Using estimates of between-study heterogeneity, we sub-classified our 24 studies into four specific clusters. We found that SPINK1 N34S is strongly associated with CP overall (OR 11.00; 95% CI: 7.59-15.93), but the effect of SPINK1 N34S in alcoholic CP (OR 4.98, 95% CI: 3.16-7.85) was significantly smaller than in idiopathic CP (OR 14.97, 95% C.I. = 9.09-24.67) or tropical CP (OR 19.15, 95% C.I. = 8.83-41.56). Studies analyzing familial CP showed very high heterogeneity suggestive of a complex etiology with an I(2) = 80.95%.

CONCLUSION : The small effect of SPINK1 N34S in alcoholic subjects suggests that CP is driven through a different pathway that is largely trypsin-independent. The results also suggest that large effect sizes of SPINK1 N34S in small candidate gene studies in CP may be related to a mixture of multiple etiologic pathways leading to the same clinical endpoint.
PMID: 18414673

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