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 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Cardiovascular Disorders
Published in: BMC Cardiovascular Disorders 1/2014

Open Access 01-12-2014 | Research article

Interaction of type 2 diabetes mellitus with Chromosome 9p21 rs10757274 polymorphism on the risk of myocardial infarction: a case–control study in Chinese population

Authors: Liu-wei Zhang, Jian-ping Li, Fang-fang Duan, Zhi-ke Liu, Si-yan Zhan, Yong-hua Hu, Jie Jiang, Yan Zhang, Yong Huo, Da-fang Chen

Published in: BMC Cardiovascular Disorders | Issue 1/2014

Login to get access

Abstract

Background

Myocardial infarction (MI) is a serious complication of Coronary Artery Disease (CAD). Previous studies have identified genetic variants on chromosome 9p21 and 6p24 that are associated with CAD, but further studies need to be conducted to investigate whether these genetic variants are associated with the pathogenesis of MI. We therefore performed this study to assess the association between the risk of MI and SNP rs10757274 on chromosome 9p21 and SNP rs6903956 on chromosome 6p24, and to explore the gene-environment interactions in a Chinese population.

Methods

A hospital-based case–control study, consisting of 502 MI patients and 308 controls, was conducted in a Chinese population. Demographic, behavioral information and clinical characteristics were collected, and genotyping of the two SNPs was performed using single base primer extension genotyping technology. The unconditional logistic regression (ULR) method was adopted to assess the association of the two SNPs with MI risk. Both generalized multifactor dimensionality reduction (GMDR) and ULR methods were applied to explore the effect of gene-environment interactions on the risk of MI.

Results

After adjusting for covariates, it was observed that SNP rs10757274 on chromosome 9p21 was significantly associated with MI. Compared with subjects carrying the AA genotype, subjects carrying the GA or GG genotypes had a higher MI risk (ORa = 1.52, 95% CI:1.06–2.19, p a = 0.0227; ORa = 2.40, 95% CI:1.51–3.81, p a = 0.0002, respectively). Furthermore, a two-factor gene-environment interaction model of CDKN2A/B (rs10757274) and type 2 diabetes mellitus (T2DM) was identified to be the best model by GMDR (p = 0.0107), with a maximum prediction accuracy of 59.18%, and a maximum Cross-validation Consistency of 10/10. By using the ULR method, additive interaction analysis found that the combined effect resulted in T2DM-positive subjects with genotype GG/GA having an MI risk 4.38 times that of T2DM-negative subjects with genotype AA (ORadd = 4.38, 95% CI:2.56–7.47, p add < 0.0001).

Conclusions

These results show that gene polymorphism of CDKN2A/B (rs10757274) is associated with MI risk in a Chinese population. Furthermore, T2DM is likely to have an interaction with CDKN2A/B (rs10757274) that contributes to the risk of MI.
Appendix
Available only for authorised users
Literature
1.
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, et al: Heart disease and stroke statistics–2014 update: a report from the American Heart Association. Circulation. 2014, 129 (3): e28-e292. 10.1161/01.cir.0000441139.02102.80.CrossRefPubMed
2.
Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ: Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006, 367 (9524): 1747-1757. 10.1016/S0140-6736(06)68770-9.CrossRefPubMed
3.
4.
Topol EJ, Smith J, Plow EF, Wang QK: Genetic susceptibility to myocardial infarction and coronary artery disease. Hum Mol Genet. 2006, 15 (Spec No 2): R117-R123.CrossRefPubMed
5.
6.
Girelli D, Martinelli N, Peyvandi F, Olivieri O: Genetic architecture of coronary artery disease in the genome-wide era: implications for the emerging “golden dozen” loci. Semin Thromb Hemost. 2009, 35 (7): 671-682. 10.1055/s-0029-1242721.CrossRefPubMed
7.
Consortium WTCC: Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007, 447 (7145): 661-678. 10.1038/nature05911.CrossRef
8.
Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T, Jonasdottir A, Sigurdsson A, Baker A, Palsson A, Masson G, Gudbjartsson DF, Magnusson KP, Andersen K, Levey AI, Backman VM, Matthiasdottir S, Jonsdottir T, Palsson S, Einarsdottir H, Gunnarsdottir S, Gylfason A, Vaccarino V, Hooper WC, Reilly MP, Granger CB, Austin H, Rader DJ, Shah SH, Quyyumi AA, Gulcher JR, et al: A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. 2007, 316 (5830): 1491-1493. 10.1126/science.1142842.CrossRefPubMed
9.
Lee JY, Lee BS, Shin DJ, Woo Park K, Shin YA, Joong Kim K, Heo L, Young Lee J, Kyoung Kim Y, Jin Kim Y, Bum Hong C, Lee SH, Yoon D, Jung Ku H, Oh IY, Kim BJ, Lee J, Park SJ, Kim J, Kawk HK, Lee JE, Park HK, Nam HY, Park HY, Shin C, Yokota M, Asano H, Nakatochi M, Matsubara T, Kitajima H, et al: A genome-wide association study of a coronary artery disease risk variant. J Hum Genet. 2013, 58 (3): 120-126. 10.1038/jhg.2012.124.CrossRefPubMed
10.
McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR, Hinds DA, Pennacchio LA, Tybjaerg-Hansen A, Folsom AR, Boerwinkle E, Hobbs HH, Cohen JC: A common allele on chromosome 9 associated with coronary heart disease. Science. 2007, 316 (5830): 1488-1491. 10.1126/science.1142447.CrossRefPubMedPubMedCentral
11.
Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, Dixon RJ, Meitinger T, Braund P, Wichmann HE, Barrett JH, Konig IR, Stevens SE, Szymczak S, Tregouet DA, Iles MM, Pahlke F, Pollard H, Lieb W, Cambien F, Fischer M, Ouwehand W, Blankenberg S, Balmforth AJ, Baessler A, Ball SG, Strom TM, Braenne I, Gieger C, Deloukas P, et al: Genomewide association analysis of coronary artery disease. N Engl J Med. 2007, 357 (5): 443-453. 10.1056/NEJMoa072366.CrossRefPubMedPubMedCentral
12.
Schunkert H, Konig IR, Kathiresan S, Reilly MP, Assimes TL, Holm H, Preuss M, Stewart AF, Barbalic M, Gieger C, Absher D, Aherrahrou Z, Allayee H, Altshuler D, Anand SS, Andersen K, Anderson JL, Ardissino D, Ball SG, Balmforth AJ, Barnes TA, Becker DM, Becker LC, Berger K, Bis JC, Boekholdt SM, Boerwinkle E, Braund PS, Brown MJ, Burnett MS, et al: Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 2011, 43 (4): 333-338. 10.1038/ng.784.CrossRefPubMedPubMedCentral
13.
Takeuchi F, Yokota M, Yamamoto K, Nakashima E, Katsuya T, Asano H, Isono M, Nabika T, Sugiyama T, Fujioka A, Awata N, Ohnaka K, Nakatochi M, Kitajima H, Rakugi H, Nakamura J, Ohkubo T, Imai Y, Shimamoto K, Yamori Y, Yamaguchi S, Kobayashi S, Takayanagi R, Ogihara T, Kato N: Genome-wide association study of coronary artery disease in the Japanese. Eur J Hum Genet. 2012, 20 (3): 333-340. 10.1038/ejhg.2011.184.CrossRefPubMed
14.
Wang F, Xu CQ, He Q, Cai JP, Li XC, Wang D, Xiong X, Liao YH, Zeng QT, Yang YZ, Cheng X, Li C, Yang R, Wang CC, Wu G, Lu QL, Bai Y, Huang YF, Yin D, Yang Q, Wang XJ, Dai DP, Zhang RF, Wan J, Ren JH, Li SS, Zhao YY, Fu FF, Huang Y, Li QX, et al: Genome-wide association identifies a susceptibility locus for coronary artery disease in the Chinese Han population. Nat Genet. 2011, 43 (4): 345-349. 10.1038/ng.783.CrossRefPubMed
15.
Assimes TL, Knowles JW, Basu A, Iribarren C, Southwick A, Tang H, Absher D, Li J, Fair JM, Rubin GD, Sidney S, Fortmann SP, Go AS, Hlatky MA, Myers RM, Risch N, Quertermous T: Susceptibility locus for clinical and subclinical coronary artery disease at chromosome 9p21 in the multi-ethnic ADVANCE study. Hum Mol Genet. 2008, 17 (15): 2320-2328. 10.1093/hmg/ddn132.CrossRefPubMedPubMedCentral
16.
Schunkert H, Gotz A, Braund P, McGinnis R, Tregouet DA, Mangino M, Linsel-Nitschke P, Cambien F, Hengstenberg C, Stark K, Blankenberg S, Tiret L, Ducimetiere P, Keniry A, Ghori MJ, Schreiber S, El Mokhtari NE, Hall AS, Dixon RJ, Goodall AH, Liptau H, Pollard H, Schwarz DF, Hothorn LA, Wichmann HE, Konig IR, Fischer M, Meisinger C, Ouwehand W, Deloukas P, et al: Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease. Circulation. 2008, 117 (13): 1675-1684. 10.1161/CIRCULATIONAHA.107.730614.CrossRefPubMedPubMedCentral
17.
Shen GQ, Li L, Rao S, Abdullah KG, Ban JM, Lee BS, Park JE, Wang QK: Four SNPs on chromosome 9p21 in a South Korean population implicate a genetic locus that confers high cross-race risk for development of coronary artery disease. Arterioscler Thromb Vasc Biol. 2008, 28 (2): 360-365.CrossRefPubMed
18.
Zhou L, Zhang X, He M, Cheng L, Chen Y, Hu FB, Wu T: Associations between single nucleotide polymorphisms on chromosome 9p21 and risk of coronary heart disease in Chinese Han population. Arterioscler Thromb Vasc Biol. 2008, 28 (11): 2085-2089. 10.1161/ATVBAHA.108.176065.CrossRefPubMed
19.
Virani SS, Brautbar A, Lee VV, MacArthur E, Morrison AC, Grove ML, Nambi V, Frazier L, Wilson JM, Willerson JT, Boerwinkle E, Ballantyne CM: Chromosome 9p21 single nucleotide polymorphisms are not associated with recurrent myocardial infarction in patients with established coronary artery disease. Circ J. 2012, 76 (4): 950-956. 10.1253/circj.CJ-11-1166.CrossRefPubMedPubMedCentral
20.
Horne BD, Carlquist JF, Muhlestein JB, Bair TL, Anderson JL: Association of variation in the chromosome 9p21 locus with myocardial infarction versus chronic coronary artery disease. Circ Cardiovasc Genet. 2008, 1 (2): 85-92. 10.1161/CIRCGENETICS.108.793158.CrossRefPubMedPubMedCentral
21.
Doria A, Wojcik J, Xu R, Gervino EV, Hauser TH, Johnstone MT, Nolan D, Hu FB, Warram JH: Interaction between poor glycemic control and 9p21 locus on risk of coronary artery disease in type 2 diabetes. JAMA. 2008, 300 (20): 2389-2397. 10.1001/jama.2008.649.CrossRefPubMedPubMedCentral
22.
Hu WL, Li SJ, Liu DT, Wang Y, Niu SQ, Yang XC, Zhang Q, Yu SZ, Jin L, Wang XF: Genetic variants on chromosome 9p21 and ischemic stroke in Chinese. Brain Res Bull. 2009, 79 (6): 431-435. 10.1016/j.brainresbull.2009.04.001.CrossRefPubMed
23.
Thygesen K, Alpert JS, White HD: Universal definition of myocardial infarction. Eur Heart J. 2007, 28 (20): 2525-2538.CrossRefPubMed
24.
World Health Organisation: Definition Diagnosis and Classification of Diabetes Mellitus and its Complications: Report of a WHO Consultation. Part 1. Diagnosis and Classification of Diabetes Mellitus. 1999, Geneva: WHO
25.
Bell PA, Chaturvedi S, Gelfand CA, Huang CY, Kochersperger M, Kopla R, Modica F, Pohl M, Varde S, Zhao R, Zhao X, Boyce-Jacino MT, Yassen A: SNPstream UHT: ultra-high throughput SNP genotyping for pharmacogenomics and drug discovery. Biotechniques. 2002, Suppl: 70-72. 74, 76–77PubMed
26.
Lou XY, Chen GB, Yan L, Ma JZ, Zhu J, Elston RC, Li MD: A generalized combinatorial approach for detecting gene-by-gene and gene-by-environment interactions with application to nicotine dependence. Am J Hum Genet. 2007, 80 (6): 1125-1137. 10.1086/518312.CrossRefPubMedPubMedCentral
27.
Andersson T, Alfredsson L, Kallberg H, Zdravkovic S, Ahlbom A: Calculating measures of biological interaction. Eur J Epidemiol. 2005, 20 (7): 575-579. 10.1007/s10654-005-7835-x.CrossRefPubMed
28.
Motterle A, Pu X, Wood H, Xiao Q, Gor S, Ng FL, Chan K, Cross F, Shohreh B, Poston RN, Tucker AT, Caulfield MJ, Ye S: Functional analyses of coronary artery disease associated variation on chromosome 9p21 in vascular smooth muscle cells. Hum Mol Genet. 2012, 21 (18): 4021-4029. 10.1093/hmg/dds224.CrossRefPubMedPubMedCentral
29.
Xie F, Chu X, Wu H, Sun W, Shen M, Yang L, Wang Y, Shi J, Huang W: Replication of putative susceptibility loci from genome-wide association studies associated with coronary atherosclerosis in Chinese Han population. PLoS ONE. 2011, 6 (6): e20833-10.1371/journal.pone.0020833.CrossRefPubMedPubMedCentral
30.
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, et al: Executive summary: heart disease and stroke statistics–2014 update: a report from the American Heart Association. Circulation. 2014, 129 (3): 399-410. 10.1161/01.cir.0000442015.53336.12.CrossRefPubMed
31.
Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L: Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case–control study. Lancet. 2004, 364 (9438): 937-952. 10.1016/S0140-6736(04)17018-9.CrossRefPubMed
32.
Fox CS: Cardiovascular disease risk factors, type 2 diabetes mellitus, and the Framingham Heart Study. Trends Cardiovasc Med. 2010, 20 (3): 90-95. 10.1016/j.tcm.2010.08.001.CrossRefPubMedPubMedCentral
33.
Wen J, Ronn T, Olsson A, Yang Z, Lu B, Du Y, Groop L, Ling C, Hu R: Investigation of type 2 diabetes risk alleles support CDKN2A/B, CDKAL1, and TCF7L2 as susceptibility genes in a Han Chinese cohort. PLoS ONE. 2010, 5 (2): e9153-10.1371/journal.pone.0009153.CrossRefPubMedPubMedCentral
34.
Krishnamurthy J, Ramsey MR, Ligon KL, Torrice C, Koh A, Bonner-Weir S, Sharpless NE: p16INK4a induces an age-dependent decline in islet regenerative potential. Nature. 2006, 443 (7110): 453-457. 10.1038/nature05092.CrossRefPubMed
35.
Rane SG, Dubus P, Mettus RV, Galbreath EJ, Boden G, Reddy EP, Barbacid M: Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in beta-islet cell hyperplasia. Nat Genet. 1999, 22 (1): 44-52. 10.1038/8751.CrossRefPubMed
36.
Tsutsui T, Hesabi B, Moons DS, Pandolfi PP, Hansel KS, Koff A, Kiyokawa H: Targeted disruption of CDK4 delays cell cycle entry with enhanced p27(Kip1) activity. Mol Cell Biol. 1999, 19 (10): 7011-7019.CrossRefPubMedPubMedCentral
37.
Dechamethakun S, Ikeda S, Arai T, Sato N, Sawabe M, Muramatsu M: Associations between the CDKN2A/B, ADTRP and PDGFD Polymorphisms and the Development of Coronary Atherosclerosis in Japanese Patients. J Atheroscler Thromb. 2014, [Epub ahead of print]
38.
Tayebi N, Ke T, Foo JN, Friedlander Y, Liu J, Heng CK: Association of single nucleotide polymorphism rs6903956 on chromosome 6p24.1 with coronary artery disease and lipid levels in different ethnic groups of the Singaporean population. Clin Biochem. 2013, 46 (9): 755-759. 10.1016/j.clinbiochem.2013.01.004.CrossRefPubMed
39.
Lu X, Wang L, Chen S, He L, Yang X, Shi Y, Cheng J, Zhang L, Gu CC, Huang J, Wu T, Ma Y, Li J, Cao J, Chen J, Ge D, Fan Z, Li Y, Zhao L, Li H, Zhou X, Chen L, Liu D, Duan X, Hao Y, Lu F, Liu Z, Yao C, Shen C, Pu X, et al: Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease. Nat Genet. 2012, 44 (8): 890-894. 10.1038/ng.2337.CrossRefPubMedPubMedCentral
40.
Guo CY, Gu Y, Li L, Jia EZ, Li CJ, Wang LS, Yang ZJ, Cao KJ, Ma WZ: Association of SNP rs6903956 on chromosome 6p24.1 with angiographical characteristics of coronary atherosclerosis in a Chinese population. PLoS ONE. 2012, 7 (8): e43732-10.1371/journal.pone.0043732.CrossRefPubMedPubMedCentral
41.
Lupu C, Zhu H, Popescu NI, Wren JD, Lupu F: Novel protein ADTRP regulates TFPI expression and function in human endothelial cells in normal conditions and in response to androgen. Blood. 2011, 118 (16): 4463-4471. 10.1182/blood-2011-05-355370.CrossRefPubMedPubMedCentral
Metadata
Title
Interaction of type 2 diabetes mellitus with Chromosome 9p21 rs10757274 polymorphism on the risk of myocardial infarction: a case–control study in Chinese population
Authors
Liu-wei Zhang
Jian-ping Li
Fang-fang Duan
Zhi-ke Liu
Si-yan Zhan
Yong-hua Hu
Jie Jiang
Yan Zhang
Yong Huo
Da-fang Chen
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2014
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/1471-2261-14-170

Other articles of this Issue 1/2014

BMC Cardiovascular Disorders 1/2014 Go to the issue

Research article

Analysis of risk factors of ST-segment elevation myocardial infarction in young patients

Research article

Prognostic significance of heart rate turbulence parameters in patients with chronic heart failure

Research article

Scarcity of atrial fibrillation in a traditional African population: a community-based study

Reviewer acknowledgement

Reviewer Acknowledgement 2013

Research article

Association of epicardial fat with left ventricular diastolic function in subjects with metabolic syndrome: assessment using 2-dimensional echocardiography

Research article

Glucose–insulin–potassium therapy in patients with acute coronary syndrome: a meta-analysis of randomized controlled trials

ACC 2024 Congress Coverage

Cardiology Video

Highlights from the ACC 2024 Congress

Watch now

Watch official videos from the ACC congress summarizing key highlights from the last year in heart failure, cardiomyopathies, valvular disease, pulmonary vascular disease, and pediatric cardiology.

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