Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

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.
ADVANCED SEARCH
Log in
Top
BMC Cardiovascular Disorders
Published in: BMC Cardiovascular Disorders 1/2015

Open Access 01-12-2015 | Research article

Correlation of single nucleotide polymorphisms in the pregnancy-associated plasma protein-A gene with carotid plaques

Authors: Shiming Zhou, Min Cui, Zegang Yin, Rui Li, Jie Zhu, Huadong Zhou

Published in: BMC Cardiovascular Disorders | Issue 1/2015

Login to get access

Abstract

Background

Pregnancy-associated plasma protein A (PAPP-A) is abundantly expressed in carotid plaques. This study investigated the association between single nucleotide polymorphisms (SNPs) of PAPP-A and the presence of carotid plaques.

Methods

A total of 408 patients with carotid plaques and 493 controls were included in the study. All subjects were Southern Chinese Han. Carotid plaques were analyzed by computer tomography angiography. PAPP-A SNPs were identified by ligase detection reaction-polymerase chain reaction analysis. The PAPP-A genotypes rs3747823, rs7020782, and rs13290387 were analyzed.

Results

The rs7020782 C allele genotype correlated with an increased risk of developing carotid plaques under the dominant, recessive, and additive models (adjusted odds ratios: 2.60, 2.36, and 3.48, respectively; P ≤ 0.001). Only C allele-carrying genotypes correlated with a significantly increased risk of carotid plaque based on studies stratified by age and sex under the dominant model. rs7020782 remained significantly associated with the risk of carotid plaque calcification after adjusting for age and potential confounders (adjusted odds ratio, 1.89; 95 % confidence interval, 1.17–3.08; P = 0.010).

Conclusions

This study found, for the first time, that the A˃C variation of rs7020782 might be an independent risk factor for carotid plaque development and calcification. The determination of such genotypes could provide a new tool for identifying individuals at high risk for carotid atherosclerosis.
Appendix
Available only for authorised users
Literature
1.
Bayes-Genis A, Schwartz RS, Lewis DA, Overgaard MT, Christiansen M, Oxvig C, et al. Insulin-like growth factor binding protein-4 protease produced by smooth muscle cells increases in the coronary artery after angioplasty. Arteriosclerosis, Thrombosis & Vascular Biology. 2001;21(3):335–41.CrossRef
2.
Boldt HB, Overgaard MT, Laursen LS, Weyer K, Sottrup-Jensen L, Oxvig C. Mutational analysis of the proteolytic domain of pregnancy-associated plasma protein-A (PAPP-A): classification as a metzincin. Biochemical Journal. 2001;358(Pt 2):359–67.CrossRefPubMedPubMedCentral
3.
Vallejo AN, Michel JJ, Bale LK, Lemster BH, Borghesi L, Conover CA. Resistance to age-dependent thymic atrophy in long-lived mice that are deficient in pregnancy-associated plasma protein A. P Natl Acad Sci USA. 2009;106(27):11252–7.CrossRef
4.
Lawrence JB, Oxvig C, Overgaard MT, Sottrup-Jensen L, Gleich GJ, Hays LG, et al. The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. P Natl Acad Sci USA. 1999;96(6):3149–53.CrossRef
5.
Bayes-Genis A, Conover CA, Overgaard MT, Bailey KR, Christiansen M, Holmes Jr DR, et al. Pregnancy-associated plasma protein A as a marker of acute coronary syndromes. N Engl J Med. 2001;345(14):1022–9.CrossRefPubMed
6.
Heeschen C, Dimmeler S, Hamm CW, Fichtlscherer S, Simoons ML, Zeiher AM. Pregnancy-associated plasma protein-A levels in patients with acute coronary syndromes: comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis. J Am Coll Cardiol. 2005;45(2):229–37.CrossRefPubMed
7.
Consuegra-Sanchez L, Fredericks S, Kaski JC. Pregnancy-associated plasma protein-A (PAPP-A) and cardiovascular risk. Atherosclerosis. 2009;203(2):346–52.CrossRefPubMed
8.
Cola C, Clementi E, Biondi-Zoccai G, Sangiorgi G. From carotid plaque biology to serologic markers of vulnerability to predict the risk of cerebrovascular events. Acta Chirurgica Belgica. 2007;107(2):129–42.PubMed
9.
Fialova L, Pileckova N, Bauer J, Soukupova J, Kalousova M, Malbohan I, et al. Pregnancy-associated plasma protein-A in patients with cerebrovascular diseases–a pilot study. Prague Med Rep. 2006;107(1):37–45.PubMed
10.
Mueller T, Dieplingerl B, Poelz W, Haltmayer M. Increased pregnancy-associated plasma protein-a as a marker for peripheral atherosclerosis: Results from the Linz peripheral arterial disease study. Clinical Chemistry. 2006;52(6):1096–103.CrossRefPubMed
11.
Aso Y, Okumura K, Wakabayashi S, Takebayashi K, Taki S, Inukai T. Elevated pregnancy-associated plasma protein-A in sera from type 2 diabetic patients with hypercholesterolemia: Associations with carotid atherosclerosis and toe-brachial index. J Clin Endocr Metab. 2004;89(11):5713–7.CrossRefPubMed
12.
Sangiorgi G, Mauriello A, Bonanno E, Oxvig C, Conover CA, Christiansen M, et al. Pregnancy-associated plasma protein-A is markedly expressed by monocyte-macrophage cells in vulnerable and ruptured carotid atherosclerotic plaques - A link between inflammation and cerebrovascular events. Journal of the American College of Cardiology. 2006;47(11):2201–11.CrossRefPubMed
13.
Heider P, Pfaffle N, Pelisek J, Wildgruber M, Poppert H, Rudelius M, et al. Is serum pregnancy-associated plasma protein a really a potential marker of atherosclerotic carotid plaque stability? European Journal of Vascular and Endovascular Surgery. 2010;39(6):668–75.CrossRefPubMed
14.
Li Y, Zhou C, Zhou X, Song L, Hui R. PAPP-A in cardiac and non-cardiac conditions. Clin Chim Acta. 2013;417:67–72.CrossRefPubMed
15.
Conover CA. Key questions and answers about pregnancy-associated plasma protein-A. Trends Endocrin Met. 2012;23(5):242–9.CrossRef
16.
Hermus L, Lefrandt JD, Tio RA, Breek JC, Zeebregts CJ. Carotid plaque formation and serum biomarkers. Atherosclerosis. 2010;213(1):21–9.CrossRefPubMed
17.
Park S, Youn JC, Shin DJ, Park CM, Kim JS, Ko YG, et al. Genetic polymorphism in the pregnancy-associated plasma protein-A associated with acute myocardial infarction. Coron Artery Dis. 2007;18(6):417–22.CrossRefPubMed
18.
Wang HP, Song Y, Zhang C, Zhan JJ, Zhang R, Wang HJ. Genetic relationship between serum pregnancy-associated plasma protein-A gene polymorphism and ischemic cerebrovascular disease in a Northern Han Chinese population. Neural Regen Res. 2012;7(7):528–33.PubMedPubMedCentral
19.
Zhao XY, Wang XF, Li L, Zhang JY, Du YY, Yao HM. Plaque characteristics and serum pregnancy-associated plasma protein A levels predict the no-reflow phenomenon after percutaneous coronary intervention. J Int Med Res. 2013;41(2):307–16
20.
de Weert TT, Ouhlous M, Meijering E, Zondervan PE, Hendriks JM, van Sambeek MRHM, et al. In vivo characterization and quantification of atherosclerotic carotid plaque components with multidetector computed tomography and histopathological correlation. Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26(10):2366–72.CrossRefPubMed
21.
Hulkkonen J. Polymorphism in the IL6 promoter region is associated with the risk factors and markers of subclinical atherosclerosis in men:The Cardiovascular Risk in Young Finns Study. Atherosclerosis. 2009;203:454–8.CrossRefPubMed
22.
Yuan J, Jin C, Qin H-D, Wang J, Sha W, Wang M, et al. Replication study confirms link between tspan18 mutation and schizophrenia in Han Chinese. PLoS ONE. 2013;8(3):e58785.CrossRefPubMedPubMedCentral
23.
Shi Y, Li Z, Xu Q, Wang T, Li T, Shen J, et al. Common variants on 8p12 and 1q24.2 confer risk of schizophrenia. Nature genetics. 2011;43(12):1224–7.CrossRefPubMedPubMedCentral
24.
Chen ZJ, Zhao H, He L, Shi Y, Qin Y, Shi Y, et al. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nature genetics. 2011;43(1):55–9.CrossRefPubMed
25.
O’Donovan MC, Craddock N, Norton N, Williams H, Peirce T, Moskvina V, et al. Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nature genetics. 2008;40(9):1053–5.CrossRefPubMed
26.
Thomas G, Sinville R, Sutton S, Farquar H, Hammer RP, Soper SA, et al. Capillary and microelectrophoretic separations of ligase detection reaction products produced from low‐abundant point mutations in genomic DNA. Electrophoresis. 2004;25(10–11):1668–77.CrossRefPubMed
27.
Djurić T, Stojković L, Zivković M, Končar I, Stanković A, Djordjević A, et al. Matrix metalloproteinase-1 promoter genotypes and haplotypes are associated with carotid plaque presence. Clinical Biochemistry. 2012;45(16–17):1353–6.CrossRefPubMed
28.
Li W, Jin X, Zhou Y, Zhu M, Lin X, Hu X, et al. Lack of independent relationship between the MMP-12 gene polymorphism and carotid plaque susceptibility in the Chinese Han population. Vasc Med. 2012;17(5):310–6.CrossRefPubMed
29.
Dong C, Beecham A, Wang L, Blanton SH, Rundek T, Sacco RL. Follow-up association study of linkage regions reveals multiple candidate genes for carotid plaque in Dominicans. Atherosclerosis. 2012;223(1):177–83.CrossRefPubMedPubMedCentral
30.
Straface G, Biscetti F, Pitocco D, Bertoletti G, Misuraca M, Vincenzoni C, et al. Assessment of the genetic effects of polymorphisms in the osteoprotegerin gene, TNFRSF11B, on serum osteoprotegerin levels and carotid plaque vulnerability. Stroke. 2011;42(11):3022–8.CrossRefPubMed
31.
O’Donnell CJ, Kavousi M, Smith AV, Kardia SLR, Feitosa MF, Hwang S-J, et al. Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction. Circulation. 2011;124(25):2855–64.CrossRefPubMedPubMedCentral
32.
Johnson AD, Hwang S-J, Voorman A, Morrison A, Peloso GM, Hsu Y-H, et al. Resequencing and clinical associations of the 9p21.3 region: a comprehensive investigation in the Framingham Heart Study. Circulation. 2013;127(7):799–810.CrossRefPubMedPubMedCentral
33.
Hofmann Bowman MA, McNally EM. Genetic pathways of vascular calcification. Trends in Cardiovascular Medicine. 2012;22(4):93–8.CrossRefPubMed
34.
Bos D, Ikram MA, Isaacs A, Verhaaren BF, Hofman A, van Duijn CM, et al. Genetic loci for coronary calcification and serum lipids relate to aortic and carotid calcification. Circ Cardiovasc Genet. 2013;6(1):47–53.CrossRefPubMed
35.
Aherrahrou Z, Schunkert H. Genetics of atherosclerosis and vascular calcification go hand-in-hand. Atherosclerosis. 2013;228(2):325–6.CrossRefPubMed
36.
Suzuki K, Sata F, Yamada H, Saijo Y, Tsuruga N, Minakami H, et al. Pregnancy-associated plasma protein-A polymorphism and the risk of recurrent pregnancy loss. J Reprod Immunol. 2006;70(1–2):99–108.CrossRefPubMed
37.
Gelber S, Sezen D, Fox N, Chasen S, Witkin S. 586: Pregnancy-associated plasma protein-A (PAPP-A) gene polymorphism and first trimester risk assessment for aneuploidy. Am J Obstet Gynecol. 2007;197(6):S169.CrossRef
38.
Li X, Liu Q, Zhou T, Zhao S, Zhou S. PAPP-A: a possible pathogenic link to the instability of atherosclerotic plaque. Med Hypotheses. 2008;70(3):597–9.CrossRefPubMed
Metadata
Title
Correlation of single nucleotide polymorphisms in the pregnancy-associated plasma protein-A gene with carotid plaques
Authors
Shiming Zhou
Min Cui
Zegang Yin
Rui Li
Jie Zhu
Huadong Zhou
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2015
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-015-0041-1

Other articles of this Issue 1/2015

BMC Cardiovascular Disorders 1/2015 Go to the issue

Research article

Association between elevated serum alanine aminotransferase and cardiometabolic risk factors in rural Chinese population: a cross-sectional study

Research article

Platelet volume indices are associated with systolic and diastolic cardiac dysfunction, and left ventricular hypertrophy

Research article

Coronary microvascular function, insulin sensitivity and body composition in predicting exercise capacity in overweight patients with coronary artery disease

Research article

The relationship between fasting plasma glucose and MPO in patients with acute coronary syndrome

Research article

Access site complications following transfemoral coronary procedures: comparison between traditional compression and angioseal vascular closure devices for haemostasis

Study protocol

Evaluation of the relationship between effervescent paracetamol and blood pressure: clinical trial

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

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

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits