The Polymorphism of Type 1 Collagen (COL1A1) Gene does not Correlate with an Increased Risk of Foot Ulcers in Patients with Diabetes Mellitus

G. Tamagno; K. Fedtke; M. Eidenmüller; J. Geks; A. Hamann; K. Langer; P. H. Kann

doi:10.1055/s-0034-1395582

Experimental and Clinical Endocrinology & Diabetes, Inhaltsverzeichnis

Exp Clin Endocrinol Diabetes 2015; 123(04): 240-245
DOI: 10.1055/s-0034-1395582

Article

The Polymorphism of Type 1 Collagen (COL1A1) Gene does not Correlate with an Increased Risk of Foot Ulcers in Patients with Diabetes Mellitus

Autor*innen

G. Tamagno^*

¹Division of Endocrinology & Diabetology, Department of Gastroenterology, Endocrinology and Metabolism, University Hospital of Giessen and Marburg – Philipp's University, Marburg, Germany
K. Fedtke^*

¹Division of Endocrinology & Diabetology, Department of Gastroenterology, Endocrinology and Metabolism, University Hospital of Giessen and Marburg – Philipp's University, Marburg, Germany
M. Eidenmüller

²Diabetology Marburg, Marburg, Germany
J. Geks

³Division of Vascular Surgery and Transplantations, Department of Visceral, Thoracic and Vascular Surgery, University Hospital of Giessen and Marburg – Philipp's University, Marburg, Germany
A. Hamann

⁴Diabetes Clinic Bad Nauheim, Bad Nauheim, Germany
K. Langer

⁵Department of Medicine II, Hospital of Darmstadt, Germany
P. H. Kann

¹Division of Endocrinology & Diabetology, Department of Gastroenterology, Endocrinology and Metabolism, University Hospital of Giessen and Marburg – Philipp's University, Marburg, Germany

Abstract

Aim: Diabetic foot syndrome (DFS) is a multifactorial debilitating complication of diabetes mellitus (DM). The identification of markers for predicting the risk of developing DFS could help and direct the efforts in the prevention to the highest risk patients. Type I collagen α1 (COL1A1) is the main component of type I collagen, the most abundant structural protein of the extracellular matrix of subcutaneous tissue. COL1A1 polymorphism has been previously investigated with regard to many clinical conditions affecting the bone or the skin. In this prospective study, we have assessed COL1A1 polymorphism in patients without and with DFS.

Patients and methods: 202 DM patients without and 103 patients with DFS have been recruited. COL1A1 polymorphism, due to a mutation affecting the zinc-finger transcription factor specific protein, has been investigated. The most relevant clinical data (HbA1c, vascular risk factors, insulin treatment) have been collected and analyzed.

Results: No statistically significant difference in the distribution of the 3 genotypes constituting COL1A1 polymorphism between patients without and with DFS has been observed. Almost all DFS patients had at least one vascular risk factor, with a high rate of arterial hypertension and dyslipidemia.

Conclusion: A multifaceted set of factors is involved in the development of DFS and only a combination of them may lead to such occurrence. In our DM patient population, COL1A1 polymorphism does not correlate with the occurrence of DFS, which appears to depend mostly on the presence of vascular risk factors. However, the impact of genetic factors affecting other components of the subcutaneous tissue cannot be excluded.

Key words

diabetes mellitus - diabetic foot - collagen - COL1A1 - polymorphism - ulcer

Volltext

Referenzen

References
1 Boulton AJ, Vileikyte L, Ragnarson-Tennvall G et al. The global burden of diabetic foot disease. Lancet 2005; 366: 1719-1724
2 Ramsey SD, Newton K, Blough D et al. Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care 1999; 22: 382-387
3 Abbott CA, Carrington AL, Ashe H et al. The North-West Diabetes Foot Care Study: incidence of, and risk factors for, new diabetic foot ulceration in a community-based patient cohort. Diabet Med 2002; 19: 377-384
4 Lavery LA, van Houtum WH, Armstrong DG. Institutionalization following diabetes-related lower extremity amputation. Am J Med 1997; 103: 383-388
5 Moulik PK, Mtonga R, Gill GV. Amputation and mortality in new-onset diabetic foot ulcers stratified by etiology. Diabetes Care 2003; 26: 491-494
6 Apelqvist J, Ragnarson-Tennvall G, Persson U et al. Diabetic foot ulcers in a multidisciplinary setting: an economic analysis of primary healing and healing with amputation. J Intern Med 1994; 235: 463-471
7 Sämann A, Tajiyeva O, Müller N et al. Prevalence of the diabetic foot syndrome at the primary care level in Germany: a cross-sectional study. Diabet Med 2008; 25: 557-563
8 Currie CJ, Morgan C, Peters JR. The epidemiology and cost of inpatient care for peripheral vascular disease, infection, neuropathy, and ulceration in diabetes. Diabetes Care 1998; 21: 42-48
9 Reiber GE, Vileikyte L, Boyko EJ et al. Causal pathways for incident lower extremity ulcers in patients with diabetes from two settings. Diabetes Care 1999; 22: 157-162
10 Calhoun JH, Overgaard KA, Stevens CM et al. Diabetic foot ulcers and infections: current concepts. Adv Skin Wound Care 2002; 15: 31-42
11 Bakker K, Apelqvist J, Schaper NC. International Working Group on Diabetic Foot Editorial Board . Practical guidelines on the management and prevention of the diabetic foot 2011. Diabetes Metab Res Rev 2012; 28 (Suppl. 01) 225-231
12 Canavan RJ, Unwin NC, Kelly WF et al. Diabetes- and nondiabetes-related lower extremity amputation incidence before and after the introduction of better organized diabetes foot care: continuous longitudinal monitoring using a standard method. Diabetes Care 2008; 31: 459-463
13 Reichard P. Risk factors for progression of microvascular complications in the Stockholm Diabetes Intervention Study (SDIS). Diabetes Res Clin Pract 1992; 16: 151-156
14 Galkowska H, Olszewsk WL, Wojewodzka U et al. Expression of apoptosis- and cell cycle-related proteins in epidermis of venous leg and diabetic foot ulcers. Surgery 2003; 134: 213-220
15 El-Mesallamy HO, Hamdy NM, Ezzat OA et al. Levels of soluble advanced glycation end product-receptors and other soluble serum markers as indicators of diabetic neuropathy in the foot. J Investig Med 2011; 59: 1233-1238
16 Ahmad J, Zubair M, Malik A et al. Cathepsin-D, adiponectin, TNF-α, IL-6 and hsCRP plasma levels in subjects with diabetic foot and possible correlation with clinical variables: a multicentric study. Foot (Edinb) 2012; 22: 194-199
17 Dinh T, Tecilazich F, Kafanas A et al. Mechanisms involved in the development and healing of diabetic foot ulceration. Diabetes 2012; 61: 2937-2947
18 Gazzaruso C, Coppola A, Montalcini T et al. Lipoprotein(a) and homocysteine as genetic risk factors for vascular and neuropathic diabetic foot in type 2 diabetes mellitus. Endocrine 2012; 41: 89-95
19 Amoli MM, Hasani-Ranjbar S, Roohipour N et al. VEGF gene polymorphism association with diabetic foot ulcer. Diabetes Res Clin Pract 2011; 93: 215-219
20 Chen SJ, Artlett CM, Jimenez SA et al. Modulation of human alpha1(I) procollagen gene activity by interaction with Sp1 and Sp3 transcription factors in vitro. Gene 1998; 215: 101-110
21 Rossert J, Terraz C, Dupont S. Regulation of type I collagen genes expression. Nephrol Dial Transplant 2000; 15 (Suppl. 06) 66-68
22 Bornstein P, McKay J, Morishima JK et al. Regulatory elements in the first intron contribute to transcriptional control of the human alpha 1(I) collagen gene. Proc Natl Acad Sci USA 1987; 84: 8869-8873
23 Grant SF, Reid DM, Blake G et al. Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene. Nat Genet 1996; 14: 203-205
24 Robinson RJ, Al Azzawi F, Iqbal SJ et al. The relation of hand skin-fold thickness to bone mineral density in patients with Crohn’s disease. Eur J Gastroenterol Hepat 1997; 9: 945-949
25 Mann V, Hobson EE, Li B et al. A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 2001; 107: 899-907
26 Kann P, Bergink AP, Fang Y et al. The collagen Ia1 SP1 polymorphism is associated with differences in ultrasound transmission velocity in the calcaneus in postmenopausal women. Calcif Tissue Int 2002; 70: 450-456
27 Ralston SH, Uitterlinden AG, Brandi ML et al. Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study. PLoS Med 2006; 3: e90
28 Hitraya EG, Varga J, Artlett CM et al. Identification of elements in the promoter region of the alpha1(I) procollagen gene involved in its up-regulated expression in systemic sclerosis. Arthritis Rheum 1998; 41: 2048-2058
29 Whitmore SE, Levine MA. Risk factors for reduced skin thickness and bone density: possible clues regarding pathophysiology, prevention, and treatment. J Am Acad Dermatol 1998; 38: 248-255
30 Saitta B, Gaidarova S, Cicchillitti L et al. CCAAT binding transcription factor binds and regulates human COL1A1 promoter activity in human dermal fibroblasts: demonstration of increased binding in systemic sclerosis fibroblasts. Arthritis Rheum 2000; 43: 2219-2229
31 Meyer S, Haist M, Schaefer S et al. Association of COLIA1 Sp1 polymorphism with the effect of subcutaneously injected recombinant hGH in GH-deficient adults. Pharmacogenomics 2008; 9: 1017-1026
32 http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ss.cgi?ss=ss12568597 (last access: 8^th August 2013).
33 Nguyen TV, Esteban LM, White CP et al. Contribution of the collagen I alpha1 and vitamin D receptor genes to the risk of hip fracture in elderly women. J Clin Endocrinol Metab 2005; 90: 6575-6579
34 Wagner FW. The dysvascular foot: a system of diagnosis and treatment. Foot Ankle 1981; 2: 64-122
35 Sun JH, Tsai JS, Huang CH et al. Risk factors for lower extremity amputation in diabetic foot disease categorized by Wagner classification. Diabetes Res Clin Pract 2012; 95: 358-363
36 Hartleb S, Plöckinger U, Stalla GK et al. Additive effect of GHRd3 and COLIA1 polymorphisms on the GH-substitution dose in GH-deficient adults. Pharmacogenomics 2011; 12: 1653-1661
37 Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215
38 http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1800012 (last access: 19^th August 2013).
39 Wang YN, Lee K, Ledoux WR. Histomorphological evaluation of diabetic and non-diabetic plantar soft tissue. Foot Ankle Int 2011; 32: 802-810
40 Ayuk SM, Houreld NN, Abrahamse H. Collagen production in diabetic wounded fibroblasts in response to low-intensity laser irradiation at 660 nm. Diabetes Technol Ther 2012; 14: 1110-1117
41 Kuivaniemi H, Tromp G, Prockop DJ. Mutations in collagen genes: causes of rare and some common diseases in humans. FASEB J 1991; 5: 2052-2060
42 Kurt-Sirin O, Yilmaz-Aydogan H, Uyar M et al. Combined effects of collagen type I alpha1 (COL1A1) Sp1 polymorphism and osteoporosis risk factors on bone mineral density in Turkish postmenopausal women. Gene 2014; 540: 226-231
43 Hampson G, Evans C, Petitt RJ et al. Bone mineral density, collagen type 1 alpha 1 genotypes and bone turnover in premenopausal women with diabetes mellitus. Diabetologia 1998; 41: 1314-1320
44 Videman T, Saarela J, Kaprio J et al. Associations of 25 structural, degradative, and inflammatory candidate genes with lumbar disc desiccation, bulging, and height narrowing. Arthritis Rheum 2009; 60: 470-481
45 Ferrari MM, Rossi G, Biondi ML et al. Type I collagen and matrix metalloproteinase 1, 3 and 9 gene polymorphisms in the predisposition to pelvic organ prolapse. Arch Gynecol Obstet 2012; 285: 1581-1586
46 Sezer S, Simşek N, Celik HT et al. Association of collagen type I alpha 1 gene polymorphism with inguinal hernia. Hernia 2014; 18: 507-512
47 Henney AM, Tsipouras P, Schwartz RC et al. Genetic evidence that mutations in the COL1A1, COL1A2, COL3A1, or COL5A2 collagen genes are not responsible for mitral valve prolapse. Br Heart J 1989; 61: 292-299
48 Ficek K, Cieszczyk P, Kaczmarczyk M et al. Gene variants within the COL1A1 gene are associated with reduced anterior cruciate ligament injury in professional soccer players. J Sci Med Sport 2013; 16: 396-400
49 Morbach S, Müller E, Reike H et al. Diabetic foot syndrome. Exp Clin Endocrinol Diabetes 2014; 122: 416-424
50 Crawford F, Inkster M, Kleijnen J et al. Predicting foot ulcers in patients with diabetes: a systematic review and meta-analysis. QJM 2007; 100: 65-86
51 Moura Neto A, Zantut-Wittmann DE, Fernandes TD et al. Risk factors for ulceration and amputation in diabetic foot: study in a cohort of 496 patients. Endocrine 2013; 44: 119-124
52 Kamenov ZA, Petrova JJ, Christov VG. Diagnosis of diabetic neuropathy using simple somatic and a new autonomic (neuropad) tests in the clinical practice. Exp Clin Endocrinol Diabetes 2010; 118: 226-233
53 Nehring P, Mrozikiewicz-Rakowska B, Krzyzewska M et al. Diabetic foot risk factors in type 2 diabetes patients: a cross-sectional case control study. J Diabetes Metab Disord 2014; 13: 79
54 Ikem R, Ikem I, Adebayo O et al. An assessment of peripheral vascular disease in patients with diabetic foot ulcer. Foot (Edinb) 2010; 20: 114-117