Detection of the 5HT2C polymorphism in myocardial infarction and cardiovascular event patients

Yıl 2019, , 243 - 249, 28.05.2019

İbrahim Açıkbaş , Buket Er Urgancı Dursun Dursunoğlu Asuman Kaftan

https://doi.org/10.31362/patd.482444

Öz

Purpose:
Deaths from cardiovascular (CV) disease are prevalent worldwide. Genetics,
environment, nutritional habits, and lifestyle
are major factors in the etiology of
Coronary artery disease (CAD). Certain genes (that
play roles in lipid, homocysteine, glucose metabolism,
renin-angiotensin, fibrinolytic, and inflammation systems) have been found in
association with CAD by genome-wide
association studies. The present genes are not important for direct and
independent prediction. A recent study on the rs6318 polymorphism of the
serotonin receptor 2C (5HT2C) gene in the prediction
of CAD and myocardial infarction (MI) can meet the expected criteria. The aim of our study is to determine the predictive and risk alleles of
the rs6318 polymorphism of the 5HT2C gene by comparing healthy subjects with
patients diagnosed with MI and CAD.

Materials and Methods:
The study consisted of two groups: 142 patients and 100 controls. DNA was
isolated from venous blood and "melting curve genotyping" analysis
was performed.

Results:
GC genotype was 4.9% in the case group and 27% in the control group. The GC
genotype is protective against CV disease (p=0.01). In addition, the
observation that no GC genotyped subjects were diagnosed with MI suggests that
the GC genotype is protective for MI in our study. Also, among cases with MI,
it was found that only 1 patient (0.9%) was CC homozygote, while there were 12
patients (11%) that were C hemizygotes. 

Conclusion:
The results suggest that the C allele has a protective effect against CV
diseases, although no clear statistical significance is found.

Anahtar Kelimeler

5HT2C, myocardial infarction, coronary artery disease, polymorphism, cardiovascular

Miyokard enfarktüsü ve kardiyovasküler olay geçiren hastalarda 5HT2C polimorfizminin saptanması

Öz

Amaç:
Kardiyovasküler hastalıklardan (KV) ölümler dünya genelinde ilk sırada yer
almaktadır. Etiyolojide genetik, çevre, beslenme ve yaşam tarzının etkileri
bulunmaktadır. Genom tarama çalışmaları, koroner arter hastalıklarıyla (KAH)
ilişkili çeşitli genler (lipid, homosistein, glukoz, metabolizmaları,
renin-anjiyotensin, fibnolitik, inflamasyon sistemlerinde rol alan genler)
ortaya çıkarmıştır. Bunların arasında tek başına direk ve bağımsız bir
prediktif faktör olarak öne çıkan yok gibidir. Son yapılan bir çalışmada 5HTR2C
genine ait rs6318 polimorfizminin, KAH ve Miyokard enfarktüs (MI) riskini
belirlemede beklenen özellikleri karşılayabileceği ortaya çıkmıştır.
Çalışmamızın amacı MI ve KAH tanısı alan hastalarda 5HTR2C genindeki rs6318
polimorfizmini belirlemek ve sağlıklı bireylerle karşılaştırarak koruyucu ve
riskli allelleri tespit etmektir.

Gereç ve
yöntem: Çalışmamız 142 hasta ve 100 kontrol olmak üzere
iki gruptan oluşmaktadır. Venöz kandan DNA izolasyonu yapıldı ve "erime
eğrisi genotiplemesi" analizi gerçekleştirildi.

Bulgular:
GC genotipi, olgu grubunda %4,9, kontrol grubunda %27 idi. GC genotipi, KV
hastalığına karşı koruyucu olarak bulundu (p=0,01). Ek olarak, GC genotipli
deneklere MI tanısı konmadığı gözlemi, çalışmamızda GC genotipinin MI için
koruyucu olduğunu düşündürdü. Ayrıca MI'lı olgularda sadece 1 hastanın (%0,9)
CC homozigot olduğu, 12'sinde (%11) ise C hemizigot olduğu saptandı.

Sonuç:
C allelinin belirgin bir istatistiksel anlamlılık olmamasına rağmen, KV
hastalıklarına karşı koruyucu bir etkiye sahip olduğunu göstermektedir.

Anahtar Kelimeler

5HT2C, Miyokard enfarktüs, Koroner arter hastalığı, Polimorfizm, Kardiyovasküler

Kaynakça

• Mathers CD, Loncar D, Boreham J, Thun M, Heath J, Doll R. Projections of Global Mortality and Burden of Disease from 2002 to 2030. Samet J, editor. PLoS Med. World Bank; 2006;3[11]:e442. Available from: http://dx.plos.org/10.1371/journal.pmed.0030442
• WHO. Global atlas on cardiovascular disease prevention and control. World Health Organization. Geneva, World Health Organization; 2017. Available from: http://www.who.int/mediacentre/factsheets/fs317/en/
• TÜİK. Türkiye İstatistik Kurumu, Ölüm Nedeni İstatistikleri, 2016. Türkiye İstatistik Kurumu. 2017. Available from: http://www.tuik.gov.tr/PreHaberBultenleri.do?id=24572
• Chico TJ, Milo M, Crossman DC. The genetics of cardiovascular disease: new insights from emerging approaches. J Pathol 2009;220[2]:186–97.
• Delles C, Mcbride MW, Padmanabhan S, Dominiczak AF. The genetics of cardiovascular disease. Trends Endocrinol Metab 2008;19[9]:309–16.
• Abbate R, Sticchi E, Fatini C. Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies. Clin Cases Miner Bone Metab. 2008;5[1]:63–6.
• Marrugat J, D’Agostino R, Sullivan L, Elosua R, Wilson P, Ordovas J, et al. An adaptation of the Framingham coronary heart disease risk function to European Mediterranean areas. J Epidemiol Community Health 2003;57[8]:634–8.
• Janssens ACJW, Aulchenko YS, Elefante S, Borsboom GJJM, Steyerberg EW, van Duijn CM. Predictive testing for complex diseases using multiple genes: Fact or fiction? Genet Med. 2006;8[7]:395–400.
• Graham I, Atar D, Borch-Johnsen K, Boysen G, Burell G, Cifkova R, et al. Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur J Cardiovasc Prev Rehabil. 2007;14[2]:E1–40.
• Ripatti S, Tikkanen E, Orho-Melander M, Havulinna AS, Silander K, Sharma A, et al. A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses. Lancet 2010;376[9750]:1393–400.
• Vaarhorst AAM, Lu Y, Heijmans BT, Dollé MET, Böhringer S, Putter H, et al. Literature-Based Genetic Risk Scores for Coronary Heart Disease Clinical Perspective. Circ Cardiovasc Genet. 2012;5[2]:202–9.
• van der Net JB, Janssens ACJW, Sijbrands EJG, Steyerberg EW. Value of genetic profiling for the prediction of coronary heart disease. Am Heart J. 2009;158[1]:105–10.
• Humphries SE, Yiannakouris N, Talmud PJ. Cardiovascular disease risk prediction using genetic information (gene scores): is it really informative? Curr Opin Lipidol. 2008;19[2]:128–32.
• Brummett BH, Babyak MA, Jiang R, Shah SH, Becker RC, Haynes C, et al. A Functional Polymorphism in the 5HTR2C Gene Associated with Stress Responses Also Predicts Incident Cardiovascular Events. Plos One 2013;8[1]:e8278.
• Abacı A. Kardiyovasküler risk faktörlerinin ülkemizdeki durumu. Türk Kardiyol Dern Arş -Arch Turk Soc Cardiol. 2011;39[4]:1–5.
• Onat A, Can G, Yüksel H, Ademoğlu E, Erginel-Ünaltuna N, Kaya A, et al. Tıp Dünyasının Kronik Hastalıklara Yaklaşımına Öncülük [Internet]. Onat A, editor. İstanbul: Lagos Yayıncılık; 2017. 20-28 p.
• Vasan RS. Biomarkers of Cardiovascular Disease. Circulation 2006;113[19]:2335–62.
• Yiannakouris N, Katsoulis M, Dilis V, Parnell LD, Trichopoulos D, Ordovas JM, et al. Genetic predisposition to coronary heart disease and stroke using an additive genetic risk score: a population-based study in Greece. Atherosclerosis 2012;222[1]:175–9.
• Hlatky MA, Chair F, Greenland P, Arnett DK, Ballantyne CM, et al. Criteria for Evaluation of Novel Markers of Cardiovascular Risk: A Scientific Statement From the American Heart Association on behalf of the American Heart Association Expert Panel on Subclinical Atherosclerotic Diseases and Emerging Risk Factors and the Stroke Council. Circulation 2009;119[17]:2408–16.
• Marrugat J, Vila J, Baena-Diez JM, Grau M, Sala J, Ramos R, et al. Relative Validity of the 10-Year Cardiovascular Risk Estimate in a Population Cohort of the REGICOR Study. Rev Esp Cardiol. 2011;64[5]:385–94.
• Han Y, Yang Y, Zhang X, Yan C, Xi S, Kang J. Relationship of the CAG repeat polymorphism of the MEF2A gene and coronary artery disease in a Chinese population. Clin Chem Lab Med. 2007;45[8]:987–92.
• O’Neil R. Role of the 5HT2c receptor in regulation of metabolism and mesolimbic dopamine. VANDERBILT Rev | Neurosci. 2010;2[1]:19–24.
• Wei Z, Wang L, Xuan J, Che R, Du J, Qin S, et al. Association analysis of serotonin receptor 7 gene [HTR7] and risperidone response in Chinese schizophrenia patients. Prog Neuro-Psychopharmacology Biol Psychiatry 2009;33[3]:547–51.
• Hoyer D, Hannon JP, Martin GR. Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav. 2002;71[4]:533–54.
• NCBI. HTR2C 5-hydroxytryptamine receptor 2C [Internet]. NCBI. 2018 [cited 2018 Jul 5]. Available from: https://www.ncbi.nlm.nih.gov/gene/3358
• Opgen-Rhein C, Brandl EJ, Müller DJ, Neuhaus AH, Tiwari AK, Sander T, et al. Association of HTR2C , but not LEP or INSIG2 , genes with antipsychotic-induced weight gain in a German sample. Pharmacogenomics 2010;11[6]:773–80.
• Bah J, Westberg L, Baghaei F, Henningsson S, Rosmond R, Melke J, et al. Further exploration of the possible influence of polymorphisms in HTR2C and 5HTT on body weight. Metabolism 2010;59[8]:1156–63.
• Brummett BH, Kuhn CM, Boyle SH, Babyak MA, Siegler IC, Williams RB. Cortisol responses to emotional stress in men: Association with a functional polymorphism in the 5HTR2C Gene. Biol Psychol. 2012;89[1]:94–8.