Article Figures & Data
Figures
- Figure 1.
Analysis of the MMP-12 rs2276109 A/G gene polymorphism by PCR-restriction fragment length polymorphism assay. A PvuII restriction endonuclease site was introduced with use of a forward mismatch primer. PCR products (199 bp) were digested with PvuII restriction enzyme and subsequently separated by 3% low-melting-point agarose gel electrophoresis with ethidium bromide staining and visualized under ultraviolet transillumination. The rs2276109 A allele resulted in 1 fragment of 199 bp, while the rs2276109 G gene variant resulted in 2 fragments of 175 bp and 24 bp. Results of a representative experiment are shown. Samples 1 and 6 have the GG genotype, samples 2, 5, and 7 have the AA genotype, and samples 3, 4, and 8 have the heterozygous AG genotype.
Tables
- Table 1.
Demographic, clinical, and serological characteristics of patients with systemic sclerosis (SSc) and control subjects. Except where indicated otherwise, values are the number (%) of subjects. Disease duration was calculated since the first non-Raynaud’s symptom and did not differ significantly among subsets of patients with SSc.
Characteristics Patients with SSc, n = 250 Controls, n = 263 Mean age, yrs ± SD 55.9 ± 12.5 54.5 ± 12.7 Sex Male 27 (10.8) 46 (17.5) Female 223 (89.2) 217 (82.5) Mean disease duration, yrs ± SD 7.7 ± 6.9 — Disease subset lcSSc 146 (58.4) — dcSSc 104 (41.6) — Autoantibody positivity ANA 227 (90.8) — Anti-topo I 77 (30.8) — ACA 91 (36.4) — Organ involvement ILD 74 (29.6) — PAH 35 (14.0) — -
ACA: anticentromere antibodies; ANA: antinuclear antibodies; anti-topo I: antitopoisomerase I antibodies; dcSSc: diffuse cutaneous SSc; ILD: interstitial lung disease; lcSSc: limited cutaneous SSc; PAH: pulmonary arterial hypertension.
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- Table 2.
Genotype distribution and allele frequency of the MMP-12 rs2276109 A/G single-nucleotide polymorphism in controls, patients with SSc, and SSc clinical subsets. Values are the number (%) of subjects with a given genotype and the frequency of the rs2276109 A allele in patients and controls.
Subjects AA AG GG A Allele Frequency Controls, n = 263 171 (65.0) 85 (32.3) 7 (2.7) 0.81 SSc, n = 250 202 (80.8) 43 (17.2) 5 (2.0)* 0.89 ** lcSSc, n = 146 108 (74.0) 35 (24.0) 3 (2.0) 0.86 dcSSc, n = 104 94 (90.4) 8 (7.7) 2 (1.9)§ 0.94§§ Anti-topo I-positive SSc, n = 77 73 (94.8) 3 (3.9) 1 (1.3) 0.97# Anti-topo I-negative SSc, n = 173 129 (74.6) 40 (23.1) 4 (2.3) 0.86 ACA-positive SSc, n = 91 64 (70.3) 25 (27.5) 2 (2.2) 0.84 ACA-negative SSc, n = 159 138 (86.8) 18 (11.3) 3 (1.9) 0.92 SSc-ILD, n = 74 67 (90.5) 5 (6.8) 2 (2.7) 0.94† SSc-non-ILD, n = 176 135 (76.7) 38 (21.6) 3 (1.7) 0.87 SSc-PAH, n = 35 31 (88.6) 4 (11.4) 0 (0.0) 0.94†† SSc-non-PAH, n = 215 171 (79.5) 39 (18.2) 5 (2.3) 0.89 -
P values calculated by chi-squared analysis.
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↵* p = 0.0003,
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↵** p = 0.0002 for comparison with controls.
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↵§ p < 0.0001 for comparison with controls and 0.003 with lcSSc;
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↵§§ p < 0.0001 for comparison with controls and 0.003 with lcSSc;
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↵# p < 0.0001 for comparison with controls and 0.0004 with anti-topo I-negative SSc;
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↵† p < 0.0001 for comparison with controls and 0.03 with SSc-non-ILD;
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↵†† p = 0.1 for comparison with SSc-non-PAH. ACA: anticentromere antibodies; anti-topo I: antitopoisomerase I antibodies; dcSSc: diffuse cutaneous SSc; ILD: interstitial lung disease; lcSSc: limited cutaneous SSc; PAH: pulmonary arterial hypertension.
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- Table 3.
Univariate analysis for association between the MMP-12 rs2276109 polymorphism and SSc clinical subsets according to recessive, dominant, and additive genetic models. Healthy controls were used as reference for all comparisons except anti-topo I-positive SSc versus anti-topo I-negative SSc, and SSc-ILD versus SSc-non-ILD.
Recessive Model Dominant Model Additive Model OR (95% CI) p OR (95% CI) p OR (95% CI) p Univariate Analysis SSc 2.26 (1.51–3.39) < 0.0001 1.34 (0.42–4.28) 0.6 1.65 (0.52–5.31) 0.4 dcSSc 5.06 (2.51–10.18) < 0.0001 1.28 (0.28–5.92) 0.7 1.68 (0.36–7.83) 0.5 lcSSc 1.53 (0.98–2.39) 0.06 1.19 (0.32–4.49) 0.8 1.22 (0.32–4.60) 0.8 Anti-topo I-positive SSc 6.22 (2.15–18.03) 0.0002 1.79 (0.20–16.36) 0.6 2.26 (0.25–20.63) 0.5 SSc-ILD 2.91 (1.24–6.83) 0.01 0.62 (0.10–3.81) 0.6 0.74 (0.12–4.56) 0.7 Multivariate Analysis* SSc 2.44 (1.61–3.71) < 0.0001 — — — — dcSSc 4.69 (2.36–9.33) < 0.0001 — — — — Anti-topo I-positive SSc 6.39 (2.18–18.76) 0.001 — — — — SSc-ILD 2.94 (1.25–6.95) 0.01 — — — — -
↵* Adjusted for age and sex. Anti-topo I: anti-topoisomerase I antibodies; dcSSc: diffuse cutaneous SSc; ILD: interstitial lung disease; lcSSc: limited cutaneous SSc.
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