Skip to main content
Top
Published in: Cardiovascular Diabetology 1/2011

Open Access 01-12-2011 | Original investigation

Low mannose-binding lectin (MBL) genotype is associated with future cardiovascular events in type 2 diabetic south asians. a prospective cohort study

Authors: Machiel A Siezenga, Prataap K Chandie Shaw, Mohamed R Daha, Ton J Rabelink, Stefan P Berger

Published in: Cardiovascular Diabetology | Issue 1/2011

Login to get access

Abstract

Background

South Asians have a high burden of type 2 diabetes and vascular complications. Vascular inflammation is considered central in the pathophysiology of atherosclerosis, and the complement system is thought to play an important role. Mannose-Binding Lectin (MBL), which activates the lectin pathway of complement activation, has been introduced as a risk marker of vascular damage. The present study explores the association of MBL levels, genotype and cardiovascular events in type 2 diabetic South Asians.

Methods

We conducted a prospective observational study. A cohort consisting of 168 type 2 diabetic South Asians was followed for a median duration of 7.66 years. At baseline, MBL levels and genotype were determined. The association with future cardiovascular events was assessed by Cox proportional hazard regression.

Results

During follow-up, 31 cardiovascular events occurred in 22 subjects (11 men, 11 women). The O/O genotype was significantly associated with the occurrence of cardiovascular events (hazard ratio 3.42, 95%CI 1.24-9.49, P = 0.018). However, log MBL levels were not associated with the occurrence of cardiovascular events (hazard ratio 0.93, 95% CI 0.50-1.73).

Conclusions

In type 2 diabetic South Asians, the O/O MBL genotype is associated with cardiovascular events, although single serum MBL levels are not.
Appendix
Available only for authorised users
Literature
1.
go back to reference Anand SS, Yusuf S: Risk factors for cardiovascular disease in Canadians of South Asian and European origin: a pilot study of the Study of Heart Assessment and Risk in Ethnic Groups (SHARE). Clin Invest Med. 1997, 20: 204-210.PubMed Anand SS, Yusuf S: Risk factors for cardiovascular disease in Canadians of South Asian and European origin: a pilot study of the Study of Heart Assessment and Risk in Ethnic Groups (SHARE). Clin Invest Med. 1997, 20: 204-210.PubMed
2.
go back to reference Forouhi NG, Sattar N, Tillin T, McKeigue PM, Chaturvedi N: Do known risk factors explain the higher coronary heart disease mortality in South Asians compared with European men? Prospective follow-up of the Southall and Brent studies, UK. Diabetologia. 2006, 49: 2580-2588. 10.1007/s00125-006-0393-2.CrossRefPubMed Forouhi NG, Sattar N, Tillin T, McKeigue PM, Chaturvedi N: Do known risk factors explain the higher coronary heart disease mortality in South Asians compared with European men? Prospective follow-up of the Southall and Brent studies, UK. Diabetologia. 2006, 49: 2580-2588. 10.1007/s00125-006-0393-2.CrossRefPubMed
3.
go back to reference Ross R: Atherosclerosis--an inflammatory disease. N Engl J Med. 1999, 115-126. 340 Ross R: Atherosclerosis--an inflammatory disease. N Engl J Med. 1999, 115-126. 340
4.
go back to reference Ostergaard J, Hansen TK, Thiel S, Flyvbjerg A: Complement activation and diabetic vascular complications. Clin Chim Acta. 2005, 361: 10-19. 10.1016/j.cccn.2005.04.028.CrossRefPubMed Ostergaard J, Hansen TK, Thiel S, Flyvbjerg A: Complement activation and diabetic vascular complications. Clin Chim Acta. 2005, 361: 10-19. 10.1016/j.cccn.2005.04.028.CrossRefPubMed
5.
go back to reference Rus HG, Niculescu F, Vlaicu R: Co-localization of terminal C5b-9 complement complexes and macrophages in human atherosclerotic arterial walls. Immunol Lett. 1988, 19: 27-32. 10.1016/0165-2478(88)90115-0.CrossRefPubMed Rus HG, Niculescu F, Vlaicu R: Co-localization of terminal C5b-9 complement complexes and macrophages in human atherosclerotic arterial walls. Immunol Lett. 1988, 19: 27-32. 10.1016/0165-2478(88)90115-0.CrossRefPubMed
6.
go back to reference Takahashi K, Ip WE, Michelow IC, Ezekowitz RA: The mannose-binding lectin: a prototypic pattern recognition molecule. Curr Opin Immunol. 2006, 18: 16-23. 10.1016/j.coi.2005.11.014.CrossRefPubMed Takahashi K, Ip WE, Michelow IC, Ezekowitz RA: The mannose-binding lectin: a prototypic pattern recognition molecule. Curr Opin Immunol. 2006, 18: 16-23. 10.1016/j.coi.2005.11.014.CrossRefPubMed
7.
go back to reference Garred P, Larsen F, Seyfarth J, Fujita R, Madsen HO: Mannose-binding lectin and its genetic variants. Genes Immun. 2006, 7: 85-94. 10.1038/sj.gene.6364283.CrossRefPubMed Garred P, Larsen F, Seyfarth J, Fujita R, Madsen HO: Mannose-binding lectin and its genetic variants. Genes Immun. 2006, 7: 85-94. 10.1038/sj.gene.6364283.CrossRefPubMed
8.
go back to reference Saevarsdottir S, Oskarsson OO, Aspelund T, Eiriksdottir G, Vikingsdottir T, Gudnason V, Valdimarsson H: Mannan binding lectin as an adjunct to risk assessment for myocardial infarction in individuals with enhanced risk. J Exp Med. 2005, 201: 117-125. 10.1084/jem.20041431.PubMedCentralCrossRefPubMed Saevarsdottir S, Oskarsson OO, Aspelund T, Eiriksdottir G, Vikingsdottir T, Gudnason V, Valdimarsson H: Mannan binding lectin as an adjunct to risk assessment for myocardial infarction in individuals with enhanced risk. J Exp Med. 2005, 201: 117-125. 10.1084/jem.20041431.PubMedCentralCrossRefPubMed
9.
go back to reference Thiel S, Holmskov U, Hviid L, Laursen SB, Jensenius JC: The Concentration of the C-Type Lectin, Mannan-Binding Protein, in Human Plasma Increases During An Acute Phase Response. Clin Exp Immunol. 1992, 90: 31-35.PubMedCentralCrossRefPubMed Thiel S, Holmskov U, Hviid L, Laursen SB, Jensenius JC: The Concentration of the C-Type Lectin, Mannan-Binding Protein, in Human Plasma Increases During An Acute Phase Response. Clin Exp Immunol. 1992, 90: 31-35.PubMedCentralCrossRefPubMed
10.
go back to reference Hansen TK, Tarnow L, Thiel S, Steffensen R, Stehouwer CD, Schalkwijk CG, Parving HH, Flyvbjerg A: Association between mannose-binding lectin and vascular complications in type 1 diabetes. Diabetes. 2004, 53: 1570-1576. 10.2337/diabetes.53.6.1570.CrossRefPubMed Hansen TK, Tarnow L, Thiel S, Steffensen R, Stehouwer CD, Schalkwijk CG, Parving HH, Flyvbjerg A: Association between mannose-binding lectin and vascular complications in type 1 diabetes. Diabetes. 2004, 53: 1570-1576. 10.2337/diabetes.53.6.1570.CrossRefPubMed
11.
go back to reference Hansen TK, Gall MA, Tarnow L, Thiel S, Stehouwer CD, Schalkwijk CG, Parving HH, Flyvbjerg A: Mannose-binding lectin and mortality in type 2 diabetes. Arch Intern Med. 2006, 166: 2007-2013. 10.1001/archinte.166.18.2007.CrossRefPubMed Hansen TK, Gall MA, Tarnow L, Thiel S, Stehouwer CD, Schalkwijk CG, Parving HH, Flyvbjerg A: Mannose-binding lectin and mortality in type 2 diabetes. Arch Intern Med. 2006, 166: 2007-2013. 10.1001/archinte.166.18.2007.CrossRefPubMed
12.
go back to reference Best LG, Davidson M, North KE, MacCluer JW, Zhang Y, Lee ET, Howard BV, DeCroo S, Ferrell RE: Prospective analysis of mannose-binding lectin genotypes and coronary artery disease in American Indians: the Strong Heart Study. Circulation. 2004, 109: 471-475. 10.1161/01.CIR.0000109757.95461.10.CrossRefPubMed Best LG, Davidson M, North KE, MacCluer JW, Zhang Y, Lee ET, Howard BV, DeCroo S, Ferrell RE: Prospective analysis of mannose-binding lectin genotypes and coronary artery disease in American Indians: the Strong Heart Study. Circulation. 2004, 109: 471-475. 10.1161/01.CIR.0000109757.95461.10.CrossRefPubMed
13.
go back to reference Chandie Shaw PK, van Es LA, Paul LC, Rosendaal FR, Souverijn JH, Vandenbroucke JP: Renal disease in relatives of Indo-Asian Type 2 diabetic patients with end-stage diabetic nephropathy. Diabetologia. 2003, 46: 618-624.PubMed Chandie Shaw PK, van Es LA, Paul LC, Rosendaal FR, Souverijn JH, Vandenbroucke JP: Renal disease in relatives of Indo-Asian Type 2 diabetic patients with end-stage diabetic nephropathy. Diabetologia. 2003, 46: 618-624.PubMed
14.
go back to reference Siezenga MA, Chandie Shaw PK, van der Geest RN, Mollness TE, Daha MR, Rabelink TJ, Berger SP: Enhanced complement activation is part of the unfavourable cardiovascular risk profile in South Asians. Clin Exp Immunol. 2009, 157: 98-103. 10.1111/j.1365-2249.2009.03959.x.PubMedCentralCrossRefPubMed Siezenga MA, Chandie Shaw PK, van der Geest RN, Mollness TE, Daha MR, Rabelink TJ, Berger SP: Enhanced complement activation is part of the unfavourable cardiovascular risk profile in South Asians. Clin Exp Immunol. 2009, 157: 98-103. 10.1111/j.1365-2249.2009.03959.x.PubMedCentralCrossRefPubMed
15.
go back to reference Roos A, Dieltjes P, Vossen RH, Daha MR, de Knijff P: Detection of three single nucleotide polymorphisms in the gene encoding mannose-binding lectin in a single pyrosequencing reaction. J Immunol Methods. 2006, 309: 108-114. 10.1016/j.jim.2005.11.017.CrossRefPubMed Roos A, Dieltjes P, Vossen RH, Daha MR, de Knijff P: Detection of three single nucleotide polymorphisms in the gene encoding mannose-binding lectin in a single pyrosequencing reaction. J Immunol Methods. 2006, 309: 108-114. 10.1016/j.jim.2005.11.017.CrossRefPubMed
16.
go back to reference Berger SP, Roos A, Mallat MJ, Fujita T, de Fijter JW, Daha MR: Association between mannose-binding lectin levels and graft survival in kidney transplantation. Am J Transplant. 2005, 5: 1361-1366. 10.1111/j.1600-6143.2005.00841.x.CrossRefPubMed Berger SP, Roos A, Mallat MJ, Fujita T, de Fijter JW, Daha MR: Association between mannose-binding lectin levels and graft survival in kidney transplantation. Am J Transplant. 2005, 5: 1361-1366. 10.1111/j.1600-6143.2005.00841.x.CrossRefPubMed
17.
go back to reference Roos A, Garred P, Wildenberg ME, Lynch NJ, Munoz JR, Zuiverloon TC, Bouwman LH, Schlagwein N, Fallaux van der Houten FC, Faber-Krol MC, Madsen HO, Schwaeble WJ, Matsushita M, Fujita T, Daha MR: Antibody-mediated activation of the classical pathway of complement may compensate for mannose-binding lectin deficiency. Eur J Immunol. 2004, 34 (9): 2589-2598. 10.1002/eji.200324401.CrossRefPubMed Roos A, Garred P, Wildenberg ME, Lynch NJ, Munoz JR, Zuiverloon TC, Bouwman LH, Schlagwein N, Fallaux van der Houten FC, Faber-Krol MC, Madsen HO, Schwaeble WJ, Matsushita M, Fujita T, Daha MR: Antibody-mediated activation of the classical pathway of complement may compensate for mannose-binding lectin deficiency. Eur J Immunol. 2004, 34 (9): 2589-2598. 10.1002/eji.200324401.CrossRefPubMed
18.
go back to reference Prasad GV, Vangala SK, Silver SA, Wong SC, Huang M, Rapi L, Nash MM, Zaltzman JS: South Asian ethnicity as a risk factor for major adverse cardiovascular events after renal transplantation. Clin J Am Soc Nephrol. 2011, 6 (1): 204-2011. 10.2215/CJN.03100410.PubMedCentralCrossRefPubMed Prasad GV, Vangala SK, Silver SA, Wong SC, Huang M, Rapi L, Nash MM, Zaltzman JS: South Asian ethnicity as a risk factor for major adverse cardiovascular events after renal transplantation. Clin J Am Soc Nephrol. 2011, 6 (1): 204-2011. 10.2215/CJN.03100410.PubMedCentralCrossRefPubMed
19.
go back to reference Fischbacher CM, Bhopal R, Povey C, Steiner M, Chalmers J, Mueller G, Jamieson J, Knowles D: Record linked retrospective cohort study of 4.6 million people exploring ethnic variations in disease: myocardial infarction in SOuth Asians. BMC Public Health. 2007, 7: 142-10.1186/1471-2458-7-142.PubMedCentralCrossRefPubMed Fischbacher CM, Bhopal R, Povey C, Steiner M, Chalmers J, Mueller G, Jamieson J, Knowles D: Record linked retrospective cohort study of 4.6 million people exploring ethnic variations in disease: myocardial infarction in SOuth Asians. BMC Public Health. 2007, 7: 142-10.1186/1471-2458-7-142.PubMedCentralCrossRefPubMed
20.
go back to reference Nijjar AP, Wang H, Dasgupta K, Rabi DM, Quan H, Khan NA: Outcomes in a diabetic population of South Asians and whites following hospitalization for acute myocardial infarction: a retrospective cohort study. Cardiovasc Diabetol. 2010, 22 (9): 4-11.CrossRef Nijjar AP, Wang H, Dasgupta K, Rabi DM, Quan H, Khan NA: Outcomes in a diabetic population of South Asians and whites following hospitalization for acute myocardial infarction: a retrospective cohort study. Cardiovasc Diabetol. 2010, 22 (9): 4-11.CrossRef
21.
go back to reference Madsen HO, Videm V, Svejgaard A, Svennevig JL, Garred P: Association of mannose-binding-lectin deficiency with severe atherosclerosis. Lancet. 1998, 352: 959-960. 10.1016/S0140-6736(05)61513-9.CrossRefPubMed Madsen HO, Videm V, Svejgaard A, Svennevig JL, Garred P: Association of mannose-binding-lectin deficiency with severe atherosclerosis. Lancet. 1998, 352: 959-960. 10.1016/S0140-6736(05)61513-9.CrossRefPubMed
22.
go back to reference Ohlenschlaeger T, Garred P, Madsen HO, Jacobsen S: Mannose-binding-lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus. N Engl J Med. 2004, 351 (5): 260-267.CrossRefPubMed Ohlenschlaeger T, Garred P, Madsen HO, Jacobsen S: Mannose-binding-lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus. N Engl J Med. 2004, 351 (5): 260-267.CrossRefPubMed
23.
go back to reference Keller TT, van Leuven SI, Meuwese MC, Wareham NJ, Luben R, Stroes ES, Hack E, Levi M, Khaw KT, Boekholdt SM: Serum levels of mannose-binding lectin and the risk of future coronary artery disease in apparently healthy men and women. Arterioscler Thromb Vasc Biol. 2006, 26: 2345-2350. 10.1161/01.ATV.0000240517.69201.77.CrossRefPubMed Keller TT, van Leuven SI, Meuwese MC, Wareham NJ, Luben R, Stroes ES, Hack E, Levi M, Khaw KT, Boekholdt SM: Serum levels of mannose-binding lectin and the risk of future coronary artery disease in apparently healthy men and women. Arterioscler Thromb Vasc Biol. 2006, 26: 2345-2350. 10.1161/01.ATV.0000240517.69201.77.CrossRefPubMed
24.
go back to reference Best LG, Ferrell RE, DeCroo S, North KE, MacCluer JW, Zhang Y, Lee ET, Howard BV, Umans J, Palmieri V, Garred P: Genetic and other factors determining mannose-binding lectin levels in American Indians: the Strong Heart Study. BMC Med Genet. 2009, 10 (5): Best LG, Ferrell RE, DeCroo S, North KE, MacCluer JW, Zhang Y, Lee ET, Howard BV, Umans J, Palmieri V, Garred P: Genetic and other factors determining mannose-binding lectin levels in American Indians: the Strong Heart Study. BMC Med Genet. 2009, 10 (5):
25.
go back to reference Tertov VV, Sobenin IA, Tonevitsky AG, Orekhov AN, Smirnov VN: Isolation of atherogenic modified (desialylated) low density lipoprotein from blood of atherosclerotic patients: separation from native lipoprotein by affinity chromatography. Biochem Biophys Res Commun. 1990, 167: 1122-1127. 10.1016/0006-291X(90)90639-5.CrossRefPubMed Tertov VV, Sobenin IA, Tonevitsky AG, Orekhov AN, Smirnov VN: Isolation of atherogenic modified (desialylated) low density lipoprotein from blood of atherosclerotic patients: separation from native lipoprotein by affinity chromatography. Biochem Biophys Res Commun. 1990, 167: 1122-1127. 10.1016/0006-291X(90)90639-5.CrossRefPubMed
26.
go back to reference Alipour A, van Oostrom AJHHM, van Wijk JPH, Verseyden C, PLokker HWM, Jukema JW, Rabelink AJ, Castro Cabezas M: Mannose binding lectin deficiency and triglyceride-rich lipoprotein metabolism in normolipidemic subjects. Atherosclerosis. 2009, 206: 444-450. 10.1016/j.atherosclerosis.2009.03.007.CrossRefPubMed Alipour A, van Oostrom AJHHM, van Wijk JPH, Verseyden C, PLokker HWM, Jukema JW, Rabelink AJ, Castro Cabezas M: Mannose binding lectin deficiency and triglyceride-rich lipoprotein metabolism in normolipidemic subjects. Atherosclerosis. 2009, 206: 444-450. 10.1016/j.atherosclerosis.2009.03.007.CrossRefPubMed
27.
go back to reference Rugonfalvi-Kiss S, Endrész V, Madsen HO, Burian K, Duba J, Prohaszka Z, Karadi I, Romics L, Gönczöl E, Füst G, Garred P: Association of Chlamydia pneumonia with coronary artery disease and its progression is dependent on the modifying effect of mannose-binding lectin. Circulation. 2002, 106: 1071-1076. 10.1161/01.CIR.0000027137.96791.6A.CrossRefPubMed Rugonfalvi-Kiss S, Endrész V, Madsen HO, Burian K, Duba J, Prohaszka Z, Karadi I, Romics L, Gönczöl E, Füst G, Garred P: Association of Chlamydia pneumonia with coronary artery disease and its progression is dependent on the modifying effect of mannose-binding lectin. Circulation. 2002, 106: 1071-1076. 10.1161/01.CIR.0000027137.96791.6A.CrossRefPubMed
28.
go back to reference Walsh MC, Bourcier T, Takahashi K, Shi L, Busche MN, Rother RP, Solomon SC, Ezekowitz AB, Stahl GL: Mannose-binding lectin is a regulator of inflammation that accompanies myocardial ischemia and reperfusion injury. J Immunol. 2005, 175: 541-546.CrossRefPubMed Walsh MC, Bourcier T, Takahashi K, Shi L, Busche MN, Rother RP, Solomon SC, Ezekowitz AB, Stahl GL: Mannose-binding lectin is a regulator of inflammation that accompanies myocardial ischemia and reperfusion injury. J Immunol. 2005, 175: 541-546.CrossRefPubMed
29.
go back to reference Collard CD, Montalto MC, Reenstra WR, Buras JA, Stahl GL: Endothelial oxidative stress activates the lectin complement pathway: role of cytokeratin 1. Am J Pathol. 2001, 159: 1045-1054. 10.1016/S0002-9440(10)61779-8.PubMedCentralCrossRefPubMed Collard CD, Montalto MC, Reenstra WR, Buras JA, Stahl GL: Endothelial oxidative stress activates the lectin complement pathway: role of cytokeratin 1. Am J Pathol. 2001, 159: 1045-1054. 10.1016/S0002-9440(10)61779-8.PubMedCentralCrossRefPubMed
30.
go back to reference Matthijsen RA, de Winther MPJ, Kuipers D, van der Made I, Weber C, Herias V, Gijbels MJJ, Buurman WA: Macrophage-specific expression of Mannose-binding lectin controls atherosclerosis in low-density lipoprotein receptor-deficient mice. Circulation. 2009, 119: 2188-2195. 10.1161/CIRCULATIONAHA.108.830661.CrossRefPubMed Matthijsen RA, de Winther MPJ, Kuipers D, van der Made I, Weber C, Herias V, Gijbels MJJ, Buurman WA: Macrophage-specific expression of Mannose-binding lectin controls atherosclerosis in low-density lipoprotein receptor-deficient mice. Circulation. 2009, 119: 2188-2195. 10.1161/CIRCULATIONAHA.108.830661.CrossRefPubMed
31.
go back to reference Garred P, Flemming Larsen, Madsen HO, Koch C: Mannose-binding lectin deficiency-revisited. Mol Immunol. 2003, 40: 73-84. 10.1016/S0161-5890(03)00104-4.CrossRefPubMed Garred P, Flemming Larsen, Madsen HO, Koch C: Mannose-binding lectin deficiency-revisited. Mol Immunol. 2003, 40: 73-84. 10.1016/S0161-5890(03)00104-4.CrossRefPubMed
Metadata
Title
Low mannose-binding lectin (MBL) genotype is associated with future cardiovascular events in type 2 diabetic south asians. a prospective cohort study
Authors
Machiel A Siezenga
Prataap K Chandie Shaw
Mohamed R Daha
Ton J Rabelink
Stefan P Berger
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2011
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-10-60

Other articles of this Issue 1/2011

Cardiovascular Diabetology 1/2011 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.