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(PCR-RFLP. J Immunol Methods 2000;234:117-22.)Tj
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[(8.)-875 (A)93.625 (wad MR, El-Gamel Ahmed, Hasleton P)]TJ
1 Tc 144.84 0 Td
(,T)Tj
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-131.314 -10 Td
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0.2 Tw -0.081 -10 Td
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[(transplantation. )7.375 (T)62.625 (ransplantation 1998;8:1014-20.)]TJ
-13.49 -10 Td
(9.)Tj
0.2 Tw 13 0 Td
(Grainger DJ, Heathcote K, Chiano M. Genetic control of the )Tj
0.469 -10 Td
(circulating concentration of transforming growth factor type\2471.)Tj
0 Tw 0.02 -10 Td
(Hum Mol Genetics 1999;8:93-7.)Tj
-17.716 -10 Td
[(10.)-875 (Cambien F, Ricard S, )-5.5 (T)31.375 (roesch A, et al. Polymorphisms of the )]TJ
0.164 Tw 17.564 -10 Td
(transforming growth factor-\2471 gene in relation to myocardial)Tj
0.2 Tw -0.08 -10 Td
(infarction and blood pressure. Hypertension 1996;28:881-7.)Tj
-17.012 -10 Td
(1)Tj
0 Tw 3.75 0 Td
[(1.)-875 (Y)]TJ
0.2 Tw 17.777 0 Td
[(okota M, Ichihara S, Lin )0.875 (T)]TJ
0 Tw 85.786 0 Td
[(-L, Nakashima N, )-43.25 (Y)124.875 (amada )6.875 (Y.)]TJ
-90.205 -10 Td
(Association of a T29)Tj
/T1_0 8 Tf
67.225 0 Td
(\325)Tj
/TT0 8 Tf
0.2 Tw 6.697 0 Td
(C polymorphism of the transforming growth)Tj
0.164 Tw -73.82 -10 Td
(factor-\2471 gene with genetic susceptibility to myocardial infarction)Tj
0 Tw -0.143 -10 Td
(in Japanese. Circulation 2000;101;2783-7.)Tj
-17.396 -10 Td
[(12.)-875 (Zhou X, )-50 (T)]TJ
0.16901 Tw 50.201 0 Td
(an FK, Stivers DN, Arnett FC. Microsatellites and )Tj
0.2 Tw -32.779 -10 Td
(intragenic polymorphisms of transforming growth factor \247 and)Tj
264.021 170 Td
(platelet-derived growth factor and their receptor genes in native)Tj
0 Tw 0.01 -10 Td
(Americans with systemic sclerosis \(scleroderma\). Arthritis Rheum)Tj
0.009 -10 Td
(2000;43:1068-73.)Tj
-17.391 -10 Td
[(13.)-875 (Y)124.875 (amada )6.875 (Y)124.875 (, Miyauchi A, )-12.25 (T)93.875 (akagi )6.75 (Y,T)-93.75 (anaka M, Mizuno M, Harada A.)]TJ
17.379 -10 Td
(Association of C-509)Tj
/T1_0 8 Tf
68.838 0 Td
(\325)Tj
/TT0 8 Tf
6.697 0 Td
[(T)-249.875 (polymorphism, alone or in combination)]TJ
-75.442 -10 Td
(with the T869)Tj
/T1_0 8 Tf
45.033 0 Td
(\325)Tj
/TT0 8 Tf
0.2 Tw 6.697 0 Td
(C polymorphism, of the transforming growth)Tj
0.172 Tw -51.82 -10 Td
(factor-\247 1 gene with bone mineral density and genetic susceptibility)Tj
0.2 Tw 0.097 -10 Td
(to osteoporosis in Japanese women. J Mol Med 2001;79:149-56.)Tj
0 Tw -17.501 -10 Td
(14.)Tj
0.2 Tw 17 0 Td
[(Suthanthiran M, Li B, Song JO, et al. )32.25 (T)]TJ
0 Tw 127.315 0 Td
(ransforming growth )Tj
-126.834 -10 Td
[(factor-\2471 hyperexpression in African-American hypertensives: )33.625 (A)]TJ
0.16901 Tw -0.16 -10 Td
(novel mediator of hypertension and/or target organ damage. Proc)Tj
0.617 Tw 0.198 -10 Td
(Natl Acad Sci USA2000;97:3479-88.)Tj
0 Tw -17.662 -10 Td
(15.)Tj
0.2 Tw 17 0 Td
[(Arkwright PD, Laurie S, Super M, Pravica )0.375 (V)]TJ
0 Tw 144.572 0 Td
[(, Schwarz MJ, )-44 (W)62.625 (ebb)]TJ
-144.028 -10 Td
[(AK, Hutchinson IV)74.625 (.)]TJ
0.2 Tw 66.283 0 Td
(TGF-\2471 genotype and accelerated decline in)Tj
0.16901 Tw -66.312 -10 Td
(lung function of patients with cystic fibrosis. Thorax 2000;)Tj
0 Tw -0.013 -10 Td
(55:459-62.)Tj
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(Sugiura, et al: TGF-\247 polymorphism in SLE)Tj
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BT
/TT0 10 Tf
53.279 472 Td
(viduals were detected as GG genotype, so they could not be)Tj
0.25 Tw 0.017 -12 Td
[(used for the polymorphism study)75.8 (.)]TJ
11.962 -12 Td
(W)Tj
2.034 Tw 8.938 0 Td
(e failed to detect a difference in the distribution of)Tj
0.89 Tw -20.945 -12 Td
(TGF\2471 polymorphism at T869C and C-509T)Tj
0 Tw 187.969 0 Td
(between SSc)Tj
1.08 Tw -187.733 -12 Td
(patients and controls in a Japanese cohort. These negative)Tj
1.705 Tw -0.055 -12 Td
(associations of TGF\2471 polymorphism confirm 2 previous)Tj
0 Tw -0.042 -12 Td
(investigations)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 108.943 403.25 Tm
(4,12)Tj
/TT0 10 Tf
2.905 Tw 1 0 0 1 120.38 400 Tm
(. One was a small population study by)Tj
0 Tw -66.91 -12 Td
(Zhou, )Tj
/TT1 10 Tf
26.798 0 Td
(et al)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 98.953 391.25 Tm
(12)Tj
/TT0 10 Tf
0.89799 Tw 1 0 0 1 108.953 388 Tm
(showing a negative association of TGF\2471, in)Tj
0 Tw -55.477 -12 Td
(the Oklahoma Choctaw native Americans, exhibiting a high)Tj
2.34801 Tw -0.188 -12 Td
(frequency of SSc. This study has been used for several)Tj
0.242 Tw 0.21 -12 Td
(genetic analyses of SSc. The second was a large population)Tj
0.91901 Tw -0.121 -12 Td
(study in 191 SSc Caucasian patients by Susol, )Tj
/TT1 10 Tf
0 Tw 194.288 0 Td
(et al)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 266.078 343.25 Tm
(4)Tj
/TT0 10 Tf
1 0 0 1 269.453 340 Tm
[(.)-325 (That)]TJ
3.541 Tw -216.175 -12 Td
(study found associations indicating a possible role for)Tj
0.274 Tw 0.024 -12 Td
(TGF\2473, \2472, and TIMP1 in genetic susceptibility to SSc and)Tj
0.485 Tw -0.05 -12 Td
(for TGF\2473 in determining the degree of cutaneous fibrosis.)Tj
3.62801 Tw 0.208 -12 Td
(Other than the above-reported negative associations of)Tj
0.235 Tw 0.022 -12 Td
(TGF\2471, a positive association was found by Crilly)Tj
/TT1 10 Tf
0 Tw 203.043 0 Td
(, et al)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 279.741 283.25 Tm
(5)Tj
/TT0 10 Tf
1 0 0 1 285.616 280 Tm
(in)Tj
-0.23 Tw -232.222 -12 Td
(89 SSc patients in a UK population. In their study, there was)Tj
1.51801 Tw -0.074 -12 Td
(no difference between diffuse and limited SSc, similar to)Tj
0 Tw 0.133 -12 Td
(our results. )Tj
11.939 -12 Td
[(T869C at codon 10 and C-509T)-300.5 (promoter polymorphism)]TJ
0.90401 Tw -11.912 -12 Td
[(were thought to be associated with TGF\2471 protein expres)1.71 (-)]TJ
0 Tw -0.045 -12 Td
(sion. In the Japanese population, the serum concentration of)Tj
0.09801 Tw 0.02 -12 Td
[(TGF\2471 was significantly higher in the C allele than in the )28.11 (T)]TJ
1.951 Tw -0.055 -12 Td
(allele at codon 10 in a study of genetic susceptibility to)Tj
0 Tw 0.01 -12 Td
(osteoporosis)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 103.41 175.25 Tm
(13)Tj
/TT0 10 Tf
2.043 Tw 1 0 0 1 114.41 172 Tm
(or myocardial infarction)Tj
/TT0 6.25 Tf
0 Tw 1.04 0 0 1.04 215.678 175.25 Tm
(11)Tj
/TT0 10 Tf
1 0 0 1 221.928 172 Tm
(.)Tj
2.043 Tw 6.75 0 Td
(The C allele at)Tj
0.17101 Tw -175.287 -12 Td
(codon 10 was more frequent in black than white Americans)Tj
-0.302 Tw 0.071 -12 Td
(with hypertension, and this allele was associated with higher)Tj
1.965 Tw 0.024 -12 Td
(levels of TGF\2471 protein and mRNA)Tj
/TT0 6.25 Tf
0 Tw 1.04 0 0 1.04 208.012 139.25 Tm
(14)Tj
/TT0 10 Tf
2.065 Tw 1 0 0 1 214.512 136 Tm
(. Otherwise, the C)Tj
0 Tw -161.071 -12 Td
(allele at codon 10 was associated with lower TGF\2471 protein)Tj
-0.048 -12 Td
(expression)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 96.163 115.25 Tm
(15)Tj
/TT0 10 Tf
0.304 Tw 1 0 0 1 105.663 112 Tm
(in patients with cystic fibrosis. Although these)Tj
0 Tw -52.368 -12 Td
[(studies )-374.8 (have )-399.7 (limitations )-373.8 (regarding )-374.5 (the )-374.7 (association )-399.4 (with)]TJ
0.87801 Tw 0.177 -12 Td
(TGF\2471 protein expression, if the hypothesis is correct that)Tj
0.24001 Tw -0.221 -12 Td
[(the C allele at codon 10 and the )27.1 (T)]TJ
0 Tw 139.377 0 Td
[(allele at C-509T)-296.6 (are high)]TJ
1.22701 Tw 124.682 396 Td
(producer alleles, our results are not incompatible with the)Tj
0.287 Tw 0.022 -12 Td
(idea that pulmonary fibrosis is found at significantly higher)Tj
0.629 Tw 0.024 -12 Td
(frequencies in these alleles. Such alleles may be a possible)Tj
1.129 Tw 0.022 -12 Td
[(risk factor for genetic susceptibility following overexpres)3 (-)]TJ
3.399 Tw 0.034 -12 Td
(sion of TGF\247 protein in SSc patients with pulmonary)Tj
0 Tw -0.047 -12 Td
(fibrosis. In contrast to the findings by Crilly )Tj
/TT1 10 Tf
177.762 0 Td
(et al)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 512.519 415.25 Tm
(5)Tj
/TT0 10 Tf
1 0 0 1 518.144 412 Tm
(in the UK)Tj
-200.77 -12 Td
(population, the negative associations in our Japanese cohort)Tj
-0.245 Tw 0.017 -12 Td
(could be due to the heterogeneity of SSc, or perhaps to some)Tj
1.52499 Tw 0.02 -12 Td
(racial difference. Otherwise, the TGF\2473 gene may be the)Tj
0.496 Tw -0.119 -12 Td
(more likely candidate for genetic susceptibility to SSc than)Tj
0 Tw 0.017 -12 Td
(the TGF\2471 gene)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 382.245 355.25 Tm
(4)Tj
/TT0 10 Tf
1 0 0 1 385.37 352 Tm
(. Further studies should be undertaken on a)Tj
-0.15199 Tw -67.986 -12 Td
(much larger cohort with accurate characterization of clinical)Tj
3.48599 Tw -0.052 -12 Td
(features including skin, lung, renal, or gastro-intestinal)Tj
0.25 Tw 0.025 -12 Td
(fibrosis in SSc patients. )Tj
/TT2 10 Tf
0 Tw -0.057 -24 Td
(REFERENCES)Tj
/TT0 8 Tf
6.986 -10 Td
(1.)Tj
0.2 Tw 13 0 Td
(Corrin B, Butcher D, McAnulty BJ, Dubois RM, Laurent GJ,)Tj
0.538 -9.75 Td
(Harrison NK. Immunohistochemical localization of transforming)Tj
0.172 Tw 0.141 -9.75 Td
(growth factor-\2471 in the lungs of patients with systemic sclerosis,)Tj
0.2 Tw -0.071 -9.75 Td
(cryptogenic fibrosing alveolitis and other lung disorders.)Tj
0 Tw -0.034 -9.75 Td
(Histopathology 1994;24:145-50. )Tj
-13.409 -10 Td
(2.)Tj
0.2 Tw 13 0 Td
[(Querfeld C, Eckes B, Huerkamp C, Krieg )32.25 (T)]TJ
0 Tw 140.807 0 Td
(, Sollberg S. Expression)Tj
0.144 Tw -140.291 -9.75 Td
(of TGF-\2471,-\2472 and -\2473 in localized and systemic scleroderma. )Tj
0 Tw -0.149 -9.75 Td
(J Dermatol Sci 1999;21:13-22. )Tj
-13.544 -9.75 Td
[(3.)-875 (Ihn H, )-18.875 (Y)93.625 (amane K, Kubo M, )-99.875 (T)93.875 (amaki K. Blockade of endogenous)]TJ
0.2 Tw 13.562 -9.75 Td
(transforming growth factor \247 signaling prevents up-regulated)Tj
0 Tw -0.05 -10 Td
(collagen synthesis in scleroderma fibroblasts. Arthritis Rheum)Tj
0.188 -9.75 Td
(2001;44:474-80. )Tj
-13.691 -9.75 Td
[(4.)-875 (Susol E, Rands AL, Herrick A, et al. Association of markers for)]TJ
0.164 Tw 13.571 -9.75 Td
(TGF\2473, TGF\2472, and TIMP1 with systemic sclerosis. Rheumatology)Tj
0 Tw -0.084 -9.75 Td
(2000;39:1332-6.)Tj
-13.391 -10 Td
[(5.)-875 (Crilly A, Hamilton J, Clark CJ, Jardine A, Madhok R. Analysis of)]TJ
0.2 Tw 13.493 -9.75 Td
(transforming growth factor \2471 gene polymorphisms in patients with)Tj
0 Tw -0.048 -9.75 Td
(systemic sclerosis. Ann Rheum Dis 2002;61:678-81. )Tj
-13.394 -10 Td
[(6.)-875 (LeRoy C, Medsger Jr )-68.625 (T)]TJ
0.2 Tw 88.816 0 Td
(A. Criteria for the classification of early)Tj
0 Tw -75.378 -10 Td
(systemic sclerosis. J Rheumatol 2001;28:1573-6.)Tj
-13.575 -10 Td
[(7.)-875 (W)62.625 (ood NAP)99.5 (,)]TJ
0.2 Tw 53.255 0 Td
(Thomson SC, Smith RM, Bidwell JL. Identification of)Tj
0.164 Tw -39.686 -10 Td
(human TGF-\2471 signal \(leader\) sequence polymorphisms by )Tj
ET
1 g
419.25 750.75 137 10.25 re
f
0 g
53.25 54.25 504 1 re
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BT
/TT1 8 Tf
0.2 Tw 423.639 36.75 Td
(The Journal of Rheumatology 2003; 30:7)Tj
0 Tw -370.352 -0.25 Td
(1522)Tj
ET
1 g
108.25 48.75 397 11.25 re
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108.75 49.25 396 10.25 re
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0 g
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/Im0 Do
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30 31 552 730 re
W n
407.25 745.75 150 25 re
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407.25 745.75 150 15.25 re
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BT
0 g
/TT1 8 Tf
54.773 714.25 Td
[(T)62.375 (able 2. )]TJ
/TT0 8 Tf
0.18201 Tw 30.072 0 Td
(TGF\2471 polymorphism between diffuse and limited SSc, or between presen\
ce or absence of pulmonary fibrosis.)Tj
51.964 -20 Td
(n)Tj
0 Tw 53.75 0 Td
(Age )Tj
61.028 0 Td
[(W)62.625 (omen/Men)-3562 (TT)-530.875 (\(%\))-1625 (TC \(%\))-1706.125 (CC \(%\))]TJ
0.35001 Tc 209.155 0 Td
(TT\(%\))Tj
0 Tc 41.016 0 Td
(TC+CC \(%\))Tj
-323.202 -10 Td
(Mean \261 SD)Tj
-123.768 -20 Td
(T869C)Tj
5.973 -10 Td
[(Diffuse SSc)-4462.625 (30)-4500 (55.3 \261 13.1)]TJ
204.682 0 Td
(22/8)Tj
56.723 0 Td
[(6 \(20.0\))-1493.75 (14 \(46.7\))-1337.5 (10 \(33.3\))-3837.5 (6 \(20.0\))-2900 (24 \(80.0\))]TJ
-261.36 -10 Td
[(Limited SSc)-4274.125 (57)-4531.25 (56.3 \261 11.0)]TJ
204.518 0 Td
(52/5)Tj
54.723 0 Td
[(17 \(29.9\))-1243.75 (24 \(42.1\))-1337.5 (16 \(28.0\))-3618.75 (17 \(29.8\))-2650 (40 \(70.2\))]TJ
-259.11 -10 Td
(Pulmonary fibrosis)Tj
5.309 -10 Td
(Presence)Tj
68.68 0 Td
[(34)-4500 (55.6 \261 12.3)]TJ
130.541 0 Td
(27/7)Tj
56.723 0 Td
[(5 \(14.7\))-1493.75 (18 \(52.9\))-1337.5 (1)31.25 (1 \(32.4\))-3868.75 (5 \(14.7\))-2900 (29 \(85.3\))]TJ
-256.11 -10 Td
(Absence)Tj
68.793 0 Td
[(53)-4531.25 (56.2 \261 11.5)]TJ
130.541 0 Td
(47/6)Tj
54.723 0 Td
[(18 \(34.0\))-1243.75 (20 \(32.7\))-1337.5 (15 \(28.3\))-3618.75 (18 \(34.0\))-2618.75 (35 \(66.0\))]TJ
-183.36 -20 Td
(n)Tj
53.75 0 Td
(Age)Tj
61.078 0 Td
[(W)62.625 (omen/Men)-3624.5 (CC \(%\))]TJ
0.39999 Tc 110.325 0 Td
[(CT\(%\))-1999.875 (TT\(%\))]TJ
0 Tc 98.231 0 Td
[(CC \(%\))-2306.25 (CT+CT)-280.875 (\(%\))]TJ
-281.437 -10 Td
(Mean \261 SD)Tj
-123.768 -20 Td
(C-509T)Tj
5.887 -10 Td
[(Diffuse SSc)-4462.625 (30)-4500 (55.3 \261 13.1)]TJ
204.432 0 Td
(22/8)Tj
56.723 0 Td
[(6 \(20.0\))-1493.75 (13 \(43.3\))-1337.5 (1)31.25 (1 \(36.7\))-3900 (6 \(20.0\))-2900 (24 \(80.0\))]TJ
-261.11 -10 Td
[(Limited SSc)-4274.125 (57)-4531.25 (56.3 \261 11.0)]TJ
204.518 0 Td
(52/5)Tj
54.723 0 Td
[(17 \(29.8\))-1243.75 (25 \(43.9\))-1337.5 (15 \(26.3\))-3618.75 (17 \(29.8\))-2650 (40 \(70.2\))]TJ
-259.36 -10 Td
(Pulmonary fibrosis)Tj
5.309 -10 Td
(Presence)Tj
68.68 0 Td
[(34)-4500 (55.6 \261 12.3)]TJ
130.541 0 Td
(27/7)Tj
56.723 0 Td
[(5 \(14.7\))-1493.75 (17 \(50.0\))-1337.5 (12 \(35.3\))-3868.75 (5 \(14.7\))-2900 (29 \(85.3\))]TJ
-255.86 -10 Td
(Absence)Tj
68.793 0 Td
[(53 )-4275 (56.2 \261 11.5)]TJ
130.491 0 Td
(47/6)Tj
54.723 0 Td
[(18 \(34.0\))-1243.75 (21 \(39.6\))-1337.5 (14 \(26.4\))-3587.5 (18 \(34.0\))-2650 (35 \(66.0\))]TJ
-265.36 -20 Td
(* p = 0.05)Tj
/T1_0 20 Tf
0.5 0 0 1 539.174 616.5 Tm
(})Tj
/TT3 8 Tf
1 0 0 1 542.327 616.5 Tm
(*)Tj
/T1_0 20 Tf
0.5 0 0 1 540.19 515.5 Tm
(})Tj
/TT3 8 Tf
1 0 0 1 543.343 515.5 Tm
(*)Tj
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54.75 707.5 503 0.5 re
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54.75 677.5 503 0.5 re
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53.75 506.5 505 0.5 re
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BT
/TT0 8 Tf
53.481 715.25 Td
(Genotype analysis.)Tj
/TT1 8 Tf
0.371 Tw 62.996 0 Td
(Genomic DNAfrom peripheral blood was isolated. )Tj
0 Tw 166.408 0 Td
(We)Tj
2.95399 Tw -229.398 -10 Td
(analyzed 2 TGF\2471 polymorphisms: T869C \(Leu10Pro\) in codon 10)Tj
0.30099 Tw -0.197 -10 Td
(\(exon1\) in the signal peptide sequence region, and C-509Tin the promot\
er)Tj
1.334 Tw 0.057 -10 Td
(region. The genotypes of these 2 loci were identified using polymerase)Tj
0.56799 Tw -0.088 -10 Td
(chain reaction-restriction fragment length polymorphism \(PCR-RFLP\), as\
)Tj
0 Tw 0.031 -10 Td
(described)Tj
/TT1 5 Tf
1.04 0 0 1.04 84.191 668 Tm
(7)Tj
/TT1 8 Tf
0.509 Tw 1 0 0 1 89.191 665.25 Tm
(\(Figure 1\). Genotype distributions in SSc patients and controls)Tj
0.866 Tw -35.732 -10 Td
[(were analyzed with Fisher)-30.125 (\325)62.5 (s exact test. )63.375 (A)-312.625 (p value < 0.05 was considered)]TJ
0 Tw -0.066 -10 Td
(statistically significant. )Tj
/TT2 10 Tf
-0.143 -22 Td
(RESULTS)Tj
/TT1 10 Tf
3.535 Tw 0.076 -12 Td
(There was no significant difference in the distribution)Tj
2.218 Tw -0.047 -12 Td
(among SSc patients and controls of either T869C or C-)Tj
0 Tw 0.2 -12 Td
[(509T)100.2 (.)]TJ
1.075 Tw 26.108 0 Td
(When comparing TC+CC \(the presence of C allele\))Tj
2.217 Tw -26.323 -12 Td
(with TT)Tj
2.42599 Tw 39.712 0 Td
(homozygous genotype in T869C, we found no)Tj
1.776 Tw -39.635 -12 Td
[(significant difference between them \(Table 1\). Moreover)53.5 (,)]TJ
0.293 Tw 0.051 -12 Td
(there was no difference between CT+TT)Tj
0.343 Tw 166.727 0 Td
[(\(the presence of )25.6 (T)]TJ
0.25 Tw -166.759 -12 Td
[(allele\) and CC homozygous in C-509T)76.6 (.)]TJ
1.52699 Tw 276.004 174.75 Td
(The distributions of these polymorphisms according to)Tj
-0.332 Tw -11.978 -12 Td
(the clinical characteristics of SSc patients are summarized in)Tj
0.027 -12 Td
(T)Tj
0 Tw 5.358 0 Td
[(able 2. )-8.1 (W)]TJ
0.136 Tw 37.929 0 Td
(e found no difference in the distribution of either)Tj
1.71201 Tw -43.415 -12 Td
(the T869C or C-509T)Tj
1.629 Tw 96.07 0 Td
(polymorphism between the diffuse)Tj
1.71001 Tw -95.978 -12 Td
(and limited type of SSc. However, the TC+CC genotype)Tj
0.59 Tw 0.091 -12 Td
(\(the presence of C allele\) in T869C, and CT+TT)Tj
0 Tw 201.1 0 Td
[(\(the pres)-86.8 (-)]TJ
0.74001 Tw -201.092 -12 Td
[(ence of )25.5 (T)-299.8 (allele\) in C-509T)-298.6 (was more frequently found in)]TJ
0.25 Tw -0.173 -12 Td
(the diffuse type, but this trend was not significant. )Tj
0.485 Tw 12.018 -12 Td
(Among 87 SSc patients, 34 patients also had pulmonary)Tj
0 Tw -11.983 -12 Td
[(fibrosis. )106.7 (A)]TJ
-0.317 Tw 43.155 0 Td
(significantly higher proportion of polymorphisms)Tj
0 Tw -43.206 -12 Td
[(in )-424.8 (T869C )-499.8 (was )]TJ
0.18201 Tc 72.608 0 Td
(recognized )Tj
0.20799 Tc 52.362 0 Td
(among )Tj
0 Tc 34.967 0 Td
(SSc )Tj
0.16701 Tc 22.562 0 Td
(patients )Tj
0 Tc 39.104 0 Td
(with)Tj
-221.472 -12 Td
[(pulmonary fibrosis carrying the TC+CC genotype \(the pres)37.5 (-)]TJ
-0.045 -12 Td
[(ence of C allele\) compared to the TT)-235.5 (homozygous genotype)]TJ
0.787 Tw 0.098 -12 Td
(\(the absence of C allele\) \(p = 0.05\). Similarly, the CT+TT)Tj
2.23199 Tw -0.081 -12 Td
[(genotype \(the presence of )26.3 (T)-474.8 (allele\) in C-509T)]TJ
0 Tw 202.624 0 Td
[(polymor)-24.7 (-)]TJ
-202.533 -12 Td
[(phism )-374.8 (with )-399.8 (pulmonary )-374.5 (fibrosis )-375 (was )-400.2 (significantly )-399 (more)]TJ
2.05701 Tw -0.11 -12 Td
[(frequent than the CC genotype \(the absence of )27.11 (T)]TJ
0 Tw 215.083 0 Td
(allele\))Tj
1.909 Tw -215.02 -12 Td
(\(p = 0.05\). However, neither the presence of C allele in)Tj
1.828 Tw -0.08 -12 Td
[(T869C or of )25.1 (T)-424.8 (allele in C-509T)-398.7 (revealed any significant)]TJ
0.25 Tw -0.107 -12 Td
(difference compared to controls. )Tj
/TT2 10 Tf
0 Tw 0.191 -24 Td
(DISCUSSION)Tj
/TT1 10 Tf
0.36501 Tw -0.117 -12 Td
(TGF\2471 has been identified as containing 7 polymorphisms:)Tj
0.339 Tw 0.019 -12 Td
(3 in the promoter regions at positions -988, -800, and -509;)Tj
-0.33 Tw 0.022 -12 Td
(one at position +72 in a non-translated region; 2 in the signal)Tj
1.922 Tw 0.015 -12 Td
(sequence at +869 \(Leu10Pro\) and +915 \(Arg25Pro\); and)Tj
-0.117 Tw -0.045 -12 Td
(one in the coding region for the precursor part not present in)Tj
0 Tw 0.024 -12 Td
[(the active form, Ile263Thr)64.6 (.)-225 (The promoter polymorphism, C-)]TJ
1.32201 Tw 0.042 -12 Td
(509T, has been recognized in linkage disequilibrium with)Tj
0 Tw 0.002 -12 Td
(T869C)Tj
/TT1 6.25 Tf
1.04 0 0 1.04 345.184 369.25 Tm
(8,9)Tj
/TT1 10 Tf
1 0 0 1 353.496 366 Tm
[(.)-400 (W)]TJ
1.823 Tw 15.188 0 Td
(e observed that 192 \(98.5%\) of 195 subjects)Tj
1.259 Tw -51.419 -12 Td
(including SSc and controls showed a linkage between the)Tj
0 Tw 0.017 -12 Td
[(T869C )-599.8 (and )-549.8 (T-509C )]TJ
0.18201 Tc 97.574 0 Td
(genotypes. )Tj
0 Tc 52.297 0 Td
(Two )Tj
0.15401 Tc 25.83 0 Td
(polymorphisms)Tj
0 Tc 1.19 Tw -175.523 -12 Td
[(between -509 and -800 also showed the linkage disequili)2.1 (-)]TJ
0 Tw 0.019 -12 Td
(brium)Tj
/TT1 6.25 Tf
1.04 0 0 1.04 341.368 321.25 Tm
(9)Tj
/TT1 10 Tf
0.929 Tw 1 0 0 1 344.743 318 Tm
[(. In other regions at -988 and codon 263, no differ)-23.6 (-)]TJ
0.19701 Tw -27.434 -12 Td
(ence in the genetic alteration was observed)Tj
/TT1 6.25 Tf
1.04 0 0 1.04 490.08 309.25 Tm
(9)Tj
/TT1 10 Tf
1 0 0 1 493.455 306 Tm
(.)Tj
0 Tw 4.75 0 Td
(Another signal)Tj
0.118 Tw -180.898 -12 Td
[(sequence at codon 25, G915C, was shown to have a signifi)-24.2 (-)]TJ
0.32899 Tw 0.022 -12 Td
(cant association with myocardial infarction, hypertension)Tj
/TT1 6.25 Tf
0 Tw 1.04 0 0 1.04 548.348 285.25 Tm
(10)Tj
/TT1 10 Tf
1 0 0 1 554.848 282 Tm
(,)Tj
1.31 Tw -237.5 -12 Td
(and fibrotic lung)Tj
/TT1 6.25 Tf
1.04 0 0 1.04 386.618 273.25 Tm
(8)Tj
/TT1 10 Tf
1.185 Tw 1 0 0 1 393.743 270 Tm
(in Caucasian populations. However, we)Tj
1.869 Tw -76.413 -12 Td
(did not detect this genetic alteration of codon 25. In the)Tj
0.61301 Tw 0.01 -12 Td
(Japanese population described previously)Tj
/TT1 6.25 Tf
0 Tw 1.04 0 0 1.04 485.523 249.25 Tm
(11)Tj
/TT1 10 Tf
0.61301 Tw 1 0 0 1 491.523 246 Tm
[(, nearly all indi)-23.7 (-)]TJ
ET
1 g
419.25 750.75 137 10.25 re
f
BT
0 g
/TT0 8 Tf
53.729 220.75 Td
(T)Tj
0 Tw 3.699 0 Td
(able 1. )Tj
/TT1 8 Tf
0.317 Tw 26.173 0 Td
(Distribution of TGF\2471 polymorphism at T869C and C-509Tin patients wit\
h systemic sclerosis \(SSc\) and controls. )Tj
52.024 -20 Td
(n)Tj
0 Tw 53.75 0 Td
(Age )Tj
61.028 0 Td
[(W)62.625 (omen/Men)-4562 (TT)-3655.875 (TC)-3687.375 (CC)]TJ
215.879 0 Td
[(TT)-4093.375 (TC+CC)]TJ
-288.821 -10 Td
(Mean \261 SD)Tj
146.982 0 Td
[(n \(%\))-2650 (n \(%\))-2743.75 (n \(%\))]TJ
137.576 0 Td
[(n \(%\))-4056.25 (n \(%\))]TJ
-408.366 -20 Td
(T869C)Tj
5.973 -10 Td
(Controls)Tj
72.059 0 Td
[(1)31.25 (10)-4281.25 (44.5 \261 18.9)]TJ
130.541 0 Td
[(68/42)-4812.375 (24 \(21.8\))-1243.75 (53 \(48.2\))-1306.25 (33 \(30.0\))-3618.75 (24 \(21.8\))-2650 (86 \(78.2\))]TJ
-202.637 -10 Td
(SSc)Tj
73.949 0 Td
[(87)-4500 (56.0 \261 11.7)]TJ
128.541 0 Td
[(74/13)-4812.375 (23 \(26.4\))-1243.75 (38 \(43.7\))-1337.5 (26 \(29.9\))-3618.75 (23 \(26.4\))-2650 (64 \(73.6\))]TJ
-126.387 -20 Td
(n)Tj
53.75 0 Td
(Age )Tj
61.028 0 Td
[(W)93.875 (omen/Men)-4530.75 (CC )-3337.5 (CT)-3749.875 (TT)]TJ
215.329 0 Td
[(CC )-3837.5 (CT+CT)]TJ
-288.421 -10 Td
(Mean \261 SD)Tj
-123.768 -20 Td
(C-509T)Tj
6.137 -10 Td
(Controls)Tj
71.809 0 Td
[(1)31.25 (10)-4281.25 (44.5 \261 18.9)]TJ
130.541 0 Td
[(68/42)-4812.375 (23 \(20.9\))-1243.75 (54 \(49.1\))-1337.5 (33 \(30.0\))-3618.75 (23 \(20.9\))-2650 (87 \(79.1\))]TJ
-202.387 -10 Td
(SSc)Tj
73.949 0 Td
[(87)-4500 (56.0 \261 11.7)]TJ
128.541 0 Td
[(74/13)-4812.375 (23 \(26.4\))-1243.75 (38 \(43.7\))-1337.5 (26 \(29.9\))-3587.5 (23 \(26.4\))-2650 (64 \(73.6\))]TJ
ET
53 214.75 504 0.5 re
f
53.5 186 502.75 0.5 re
f
53.5 114 504 0.5 re
f
53.5 72.25 504 0.5 re
f
q
207.25 0 0 124.75 84.25 364 cm
/Im0 Do
Q
BT
/TT0 8 Tf
54.314 350.25 Td
(Figure 1.)Tj
/TT1 8 Tf
31.192 0 Td
[(Ethidium bromide-stained 4% agarose gel showing the represen)73.75 (-)]TJ
0.29401 Tw -31.044 -10 Td
(tative determination of TGF\2471 polymorphism of T869C in codon 10, and)Tj
0 Tw -0.204 -10 Td
(C-509T)Tj
0.461 Tw 27.387 0 Td
[(in the promoter region using PCR-RFLP)125.875 (.)-250 (After digestion of PCR)]TJ
0.57401 Tw -27.314 -10 Td
[(products \(294 bp\) by MspA1 in T869C \(codon 10\), )0.25 (T)]TJ
0.60201 Tw 178.759 0 Td
(allele and C allele)Tj
0.664 Tw -178.668 -10 Td
[(were characterized by a 161 bp and 149 bp fragment, respectively)66.125 (.)]TJ
0 Tw 220.935 0 Td
(After)Tj
0.11 Tw -220.871 -10 Td
(digestion of PCR products \(265 bp\) by Bsu36 in C-509T, the C allele wa\
s)Tj
0.62399 Tw -0.139 -10 Td
[(represented by a 195 bp fragment, and undigested )33.4875 (T)-343.625 (allele was shown at)]TJ
1.83299 Tw -0.072 -10 Td
(265 bp. Three genotypes in T869C \(codon 10\) were determined, i.e.,)Tj
0.541 Tw 0.046 -10 Td
(homozygous for alleles TT)Tj
0.588 Tw 90.543 0 Td
[(and CC, and heterozygous for TC. The poly)1.25 (-)]TJ
0.132 Tw -90.582 -10 Td
(morphism in C-509Twas also determined, i.e., homozygous for the alleles)Tj
-0.121 Tw 0.001 -10 Td
(CC and TT, and heterozygous for CT. MW: 50 bp ladder of molecular size)Tj
0 Tw 0.136 -10 Td
(markers; Cont.: undigested amplicon.)Tj
ET
q
0 g
237 0 0 150.75 49.25 364 cm
/Im1 Do
Q
q
30 31 552 730 re
W n
1 g
407.25 745.75 150 25 re
f
407.25 745.75 150 15.25 re
f
0 g
53.25 54.25 504 1 re
f
BT
/TT0 8 Tf
0.2 Tw 53.97 36.75 Td
(Sugiura, et al: TGF-\247 polymorphism in SLE)Tj
0 Tw 487.309 -0.25 Td
(1521)Tj
ET
1 g
108.25 48.75 397 11.25 re
f
108.75 49.25 396 10.25 re
f
q
0 g
397 0 0 11.25 108.25 48.75 cm
/Im2 Do
Q
Q
q
0 0 612 792 re
W n
BT
0 0 0 rg
/TT3 8 Tf
117.48 51 Td
(Personal, non-commercial use only. The Journal of Rheumatology Copyrig\
ht \251 2003. All rights reserved.)Tj
ET
Q
BT
/T1_0 1 Tf
10 0 0 10 540 17 Tm
( )Tj
0 0.48627 0.77255 rg
-7.22298 0 Td
(www.jrheum.org)Tj
0 g
-16.72996 0 Td
(Downloaded on March 30, 2024 from )Tj
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