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Exp Clin Endocrinol Diabetes 2015; 123(04): 240-245
DOI: 10.1055/s-0034-1395582
Article
© Georg Thieme Verlag KG Stuttgart · New York

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   *
1   Division of Endocrinology & Diabetology, Department of Gastroenterology, Endocrinology and Metabolism, University Hospital of Giessen and Marburg – Philipp's University, Marburg, Germany
,
K. Fedtke   *
1   Division of Endocrinology & Diabetology, Department of Gastroenterology, Endocrinology and Metabolism, University Hospital of Giessen and Marburg – Philipp's University, Marburg, Germany
,
M. Eidenmüller
2   Diabetology Marburg, Marburg, Germany
,
J. Geks
3   Division 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
4   Diabetes Clinic Bad Nauheim, Bad Nauheim, Germany
,
K. Langer
5   Department of Medicine II, Hospital of Darmstadt, Germany
,
P. H. Kann
1   Division of Endocrinology & Diabetology, Department of Gastroenterology, Endocrinology and Metabolism, University Hospital of Giessen and Marburg – Philipp's University, Marburg, Germany
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Publikationsverlauf

received 06. Juni 2014
first decision 09. Oktober 2014

accepted 05. November 2014

Publikationsdatum:
11. Dezember 2014 (online)

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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

* Equal contribution.


 

  • References

  • 1 Boulton AJ, Vileikyte L, Ragnarson-Tennvall G et al. The global burden of diabetic foot disease. Lancet 2005; 366: 1719-1724
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 4 Lavery LA, van Houtum WH, Armstrong DG. Institutionalization following diabetes-related lower extremity amputation. Am J Med 1997; 103: 383-388
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 10 Calhoun JH, Overgaard KA, Stevens CM et al. Diabetic foot ulcers and infections: current concepts. Adv Skin Wound Care 2002; 15: 31-42
    CrossrefPubMedSuche in Google Scholar
  • 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
    Suche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 21 Rossert J, Terraz C, Dupont S. Regulation of type I collagen genes expression. Nephrol Dial Transplant 2000; 15 (Suppl. 06) 66-68
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 32 http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ss.cgi?ss=ss12568597 (last access: 8th August 2013).
    PubMed
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 34 Wagner FW. The dysvascular foot: a system of diagnosis and treatment. Foot Ankle 1981; 2: 64-122
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 38 http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1800012 (last access: 19th August 2013).
    PubMed
  • 39 Wang YN, Lee K, Ledoux WR. Histomorphological evaluation of diabetic and non-diabetic plantar soft tissue. Foot Ankle Int 2011; 32: 802-810
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 49 Morbach S, Müller E, Reike H et al. Diabetic foot syndrome. Exp Clin Endocrinol Diabetes 2014; 122: 416-424
    Thieme ConnectPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    Thieme ConnectPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar