|
|
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result sql = Association of interleukin-1 receptor-associated kinase M (IRAK-M) and inflammatory bowel diseases.
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char = N;code = 78
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char = p;code = 112
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char = m;code = 109
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char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
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 = 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 = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
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 = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
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 = s;code = 115
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = .;code = 46
char = ;code = 32
char = R;code = 82
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = C;code = 67
char = A;code = 65
char = R;code = 82
char = D;code = 68
char = 1;code = 49
char = 5;code = 53
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = R;code = 82
char = 7;code = 55
char = 0;code = 48
char = 2;code = 50
char = W;code = 87
char = ,;code = 44
char = ;code = 32
char = G;code = 71
char = 9;code = 57
char = 0;code = 48
char = 8;code = 56
char = R;code = 82
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = 0;code = 48
char = 7;code = 55
char = f;code = 102
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = C;code = 67
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 = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = N;code = 78
char = o;code = 111
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 = ;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 = c;code = 99
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = I;code = 73
char = R;code = 82
char = A;code = 65
char = K;code = 75
char = -;code = 45
char = M;code = 77
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = d;code = 100
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 = I;code = 73
char = B;code = 66
char = D;code = 68
char = ,;code = 44
char = ;code = 32
char = U;code = 85
char = C;code = 67
char = ,;code = 44
char = ;code = 32
char = C;code = 67
char = D;code = 68
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = D;code = 68
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = U;code = 85
char = C;code = 67
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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 = 46
char = ;code = 32
char = F;code = 70
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 3;code = 51
char = 6;code = 54
char = ;code = 32
char = U;code = 85
char = C;code = 67
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = 1;code = 49
char = 3;code = 51
char = .;code = 46
char = 9;code = 57
char = %;code = 37
char = );code = 41
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 = B;code = 66
char = D;code = 68
char = -;code = 45
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 = C;code = 67
char = A;code = 65
char = R;code = 82
char = D;code = 68
char = 1;code = 49
char = 5;code = 53
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = i;code = 105
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = 2;code = 50
char = /;code = 47
char = 1;code = 49
char = 6;code = 54
char = 7;code = 55
char = ;code = 32
char = (;code = 40
char = 1;code = 49
char = .;code = 46
char = 2;code = 50
char = %;code = 37
char = );code = 41
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = -;code = 45
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = i;code = 105
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = O;code = 79
char = R;code = 82
char = ;code = 32
char = 1;code = 49
char = 3;code = 51
char = .;code = 46
char = 1;code = 49
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 = 32
char = 1;code = 49
char = .;code = 46
char = 0;code = 48
char = -;code = 45
char = 1;code = 49
char = 6;code = 54
char = 4;code = 52
char = .;code = 46
char = 5;code = 53
char = );code = 41
char = .;code = 46
char = ;code = 32
char = N;code = 78
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = C;code = 67
char = D;code = 68
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 = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = N;code = 78
char = o;code = 111
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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 = o;code = 111
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 = ;code = 32
char = a;code = 97
char = n;code = 110
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 = i;code = 105
char = o;code = 111
char = n;code = 110
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 = I;code = 73
char = B;code = 66
char = D;code = 68
char = ,;code = 44
char = ;code = 32
char = C;code = 67
char = D;code = 68
char = ,;code = 44
char = ;code = 32
char = U;code = 85
char = C;code = 67
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = D;code = 68
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = U;code = 85
char = C;code = 67
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = I;code = 73
char = R;code = 82
char = A;code = 65
char = K;code = 75
char = -;code = 45
char = M;code = 77
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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 = 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 = I;code = 73
char = R;code = 82
char = A;code = 65
char = K;code = 75
char = -;code = 45
char = M;code = 77
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = A;code = 65
char = R;code = 82
char = D;code = 68
char = 1;code = 49
char = 5;code = 53
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = U;code = 85
char = C;code = 67
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = C;code = 67
char = A;code = 65
char = R;code = 82
char = D;code = 68
char = 1;code = 49
char = 5;code = 53
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = I;code = 73
char = R;code = 82
char = A;code = 65
char = K;code = 75
char = -;code = 45
char = M;code = 77
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = t;code = 116
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
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 = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = e;code = 101
char = d;code = 100
char = e;code = 101
char = d;code = 100
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 = w;code = 119
char = h;code = 104
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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 = T;code = 84
char = L;code = 76
char = R;code = 82
char = -;code = 45
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
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 = m;code = 109
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = t;code = 116
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = l;code = 108
char = y;code = 121
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result sql = OBJECTIVE : Inflammatory bowel diseases (IBD) have a complex genetic background. The interleukin receptor associated kinase-M (IRAK-M) is a NF-kappaB-mediated, negative regulator of Toll-like receptor (TLR) signaling. A functional mutation in a negative regulator might induce impaired endotoxin tolerance and increased inflammatory responses. IRAK-M is situated on chromosome 12q14, a susceptibility locus for IBD, which makes it a good candidate gene. The objective of the study was to analyze a large cohort of IBD patients for the association between IBD and IRAK-M.
MATERIAL AND METHODS : A total of 542 patients with IBD (309 Crohn's disease (CD), 233 ulcerative colitis (UC)) and 305 controls were studied. Two single nucleotide polymorphisms (V147I and V270I) and six microsatellite markers were evaluated using association analysis and the haplotype sharing statistic. Results were stratified for CARD15 mutations R702W, G908R and 1007fsinsC.
RESULTS : No significant differences in IRAK-M allele frequencies were observed between IBD, UC, CD or subgroups of CD or UC and controls. Five out of 36 UC patients (13.9%) with an IBD-associated CARD15 mutation were carriers versus 2/167 (1.2%) in non-carriers (OR 13.1, 95% CI 1.0-164.5). No interaction was observed for CD.
CONCLUSIONS : No evidence was found to suggest an association between IBD, CD, UC or subsets of CD and UC and IRAK-M. However, an interaction was found between IRAK-M and CARD15 in UC patients. In CARD15 mutant patients, the production of IRAK-M upon stimulation might be impaired. Further studies are needed to determine whether an impaired negative regulation of the TLR-signaling pathway might be partly responsible for the development of IBD.
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result sql = Association of interleukin-1 receptor-associated kinase M (IRAK-M) and inflammatory bowel diseases.
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result sql = OBJECTIVE : Inflammatory bowel diseases (IBD) have a complex genetic background. The interleukin receptor associated kinase-M (IRAK-M) is a NF-kappaB-mediated, negative regulator of Toll-like receptor (TLR) signaling. A functional mutation in a negative regulator might induce impaired endotoxin tolerance and increased inflammatory responses. IRAK-M is situated on chromosome 12q14, a susceptibility locus for IBD, which makes it a good candidate gene. The objective of the study was to analyze a large cohort of IBD patients for the association between IBD and IRAK-M.
MATERIAL AND METHODS : A total of 542 patients with IBD (309 Crohn's disease (CD), 233 ulcerative colitis (UC)) and 305 controls were studied. Two single nucleotide polymorphisms (V147I and V270I) and six microsatellite markers were evaluated using association analysis and the haplotype sharing statistic. Results were stratified for CARD15 mutations R702W, G908R and 1007fsinsC.
RESULTS : No significant differences in IRAK-M allele frequencies were observed between IBD, UC, CD or subgroups of CD or UC and controls. Five out of 36 UC patients (13.9%) with an IBD-associated CARD15 mutation were carriers versus 2/167 (1.2%) in non-carriers (OR 13.1, 95% CI 1.0-164.5). No interaction was observed for CD.
CONCLUSIONS : No evidence was found to suggest an association between IBD, CD, UC or subsets of CD and UC and IRAK-M. However, an interaction was found between IRAK-M and CARD15 in UC patients. In CARD15 mutant patients, the production of IRAK-M upon stimulation might be impaired. Further studies are needed to determine whether an impaired negative regulation of the TLR-signaling pathway might be partly responsible for the development of IBD.
Publication: Scand. J. Gastroenterol. 2007 Jul ;42(7)::827-33.
Publication Date: 2007 Jul
Study Author(s): Weersma, Rinse K;Oostenbrug, Liekele E;Nolte, Ilja M;Van Der Steege, Gerrit;Oosterom, Elvira;Van Dullemen, Hendrik M;Kleibeuker, Jan H;Dijkstra, Gerard;
Institution: Department of Gastroenterology and Hepatology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands. [email protected]
Shortcut link to this study:
Publication Date: 2007 Jul
Study Author(s): Weersma, Rinse K;Oostenbrug, Liekele E;Nolte, Ilja M;Van Der Steege, Gerrit;Oosterom, Elvira;Van Dullemen, Hendrik M;Kleibeuker, Jan H;Dijkstra, Gerard;
Institution: Department of Gastroenterology and Hepatology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands. [email protected]
Shortcut link to this study:
OBJECTIVE : Inflammatory bowel diseases (IBD) have a complex genetic background. The interleukin receptor associated kinase-M (IRAK-M) is a NF-kappaB-mediated, negative regulator of Toll-like receptor (TLR) signaling. A functional mutation in a negative regulator might induce impaired endotoxin tolerance and increased inflammatory responses. IRAK-M is situated on chromosome 12q14, a susceptibility locus for IBD, which makes it a good candidate gene. The objective of the study was to analyze a large cohort of IBD patients for the association between IBD and IRAK-M.
MATERIAL AND METHODS : A total of 542 patients with IBD (309 Crohn's disease (CD), 233 ulcerative colitis (UC)) and 305 controls were studied. Two single nucleotide polymorphisms (V147I and V270I) and six microsatellite markers were evaluated using association analysis and the haplotype sharing statistic. Results were stratified for CARD15 mutations R702W, G908R and 1007fsinsC.
RESULTS : No significant differences in IRAK-M allele frequencies were observed between IBD, UC, CD or subgroups of CD or UC and controls. Five out of 36 UC patients (13.9%) with an IBD-associated CARD15 mutation were carriers versus 2/167 (1.2%) in non-carriers (OR 13.1, 95% CI 1.0-164.5). No interaction was observed for CD.
CONCLUSIONS : No evidence was found to suggest an association between IBD, CD, UC or subsets of CD and UC and IRAK-M. However, an interaction was found between IRAK-M and CARD15 in UC patients. In CARD15 mutant patients, the production of IRAK-M upon stimulation might be impaired. Further studies are needed to determine whether an impaired negative regulation of the TLR-signaling pathway might be partly responsible for the development of IBD.
MATERIAL AND METHODS : A total of 542 patients with IBD (309 Crohn's disease (CD), 233 ulcerative colitis (UC)) and 305 controls were studied. Two single nucleotide polymorphisms (V147I and V270I) and six microsatellite markers were evaluated using association analysis and the haplotype sharing statistic. Results were stratified for CARD15 mutations R702W, G908R and 1007fsinsC.
RESULTS : No significant differences in IRAK-M allele frequencies were observed between IBD, UC, CD or subgroups of CD or UC and controls. Five out of 36 UC patients (13.9%) with an IBD-associated CARD15 mutation were carriers versus 2/167 (1.2%) in non-carriers (OR 13.1, 95% CI 1.0-164.5). No interaction was observed for CD.
CONCLUSIONS : No evidence was found to suggest an association between IBD, CD, UC or subsets of CD and UC and IRAK-M. However, an interaction was found between IRAK-M and CARD15 in UC patients. In CARD15 mutant patients, the production of IRAK-M upon stimulation might be impaired. Further studies are needed to determine whether an impaired negative regulation of the TLR-signaling pathway might be partly responsible for the development of IBD.
PMID: 17558906
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