Coronary Artery Disease, Autosomal Dominant, 1

Description

Coronary artery disease (CAD) is a compound disorder which generates reduced or absent blood flow in one or more of the arteries that encircle and supply the heart. Its name is derived from the way the arteries sit on the heart, it can be focal or diffuse and it is the leading cause of death in developing countries where epidemiological studies emphasize dietary and environmental contributions to the disorder. Generally, CAD is a degenerative disorder and, aside from rare congenital abnormalities, it is uncommon as a clinical problem before the age of 30 years and common by the age of 60 years. One in 4 subjects will suffer from a heart attack. When symptoms indicate the potential of a heart attack, an electrocardiogram should be employed punctually, with continual observation for arrhythmia or ischemia (impaired blood supply).

Molecular Genetics

A form of autosomal dominant coronary artery disease with myocardial infarction (ADCAD1) may be related to mutation in the MEF2A gene. Another form of autosomal dominant coronary artery disease (ADCAD2) is caused by mutations in the low density lipoprotein receptor-related protein 6 (LRP6) gene, which is vital for the Wnt/beta signaling pathway through performing as a co-receptor jointly with Frizzled for Wnt. LRP6 protein consists of 1613 amino acids and has a molecular weight of 180,443 kDa.

Epidemiology in the Arab World

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Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
608320.G.1Lebanon Coronary artery stenosisNM_001242648.2:c.251-149640A>CAutosomal, DominantHager et al. 2012 Study on 1949 patien...
608320.G.2.1United Arab EmiratesUnknown Myocardial infarction; Abnormal coronar...NM_000237.2:c.776-172G>A, NR_135674.1:n.45+8018T>COsman et al. 2020 160 subjects with CA...
608320.G.2.3United Arab EmiratesUnknown Myocardial infarction; Abnormal coronar...NM_018256.3:c.1195-225A>G, NM_000237.2:c.776-172G>A, NR_135674.1:n.45+8018T>C, NM_000235.3:c.229+2506G>A, NM_000301.3:c.1256+9T>C, NG_006669.2:g.1491=, NC_000011.10:g.103789839=, NM_000235.3:c.230-954=, NC_000021.9:g.34223520A>G, NM_001321868.1:c.*1090T>C, NM_003761.4:c.*143T>C, NC_000001.11:g.55030366T>C, NC_000004.12:g.147472512C>T, NM_173598.4:c.385+27792A>C, NC_000002.12:g.21065449=, NR_033870.2:n.464-26926=, NM_001846.2:c.181-27458T>C, NM_001085049.2:c.*1011C>T, NM_001350001.1:c.714G>A, NM_001846.2:c.99+473=, NM_001645.3:c.*459A>G, NC_000001.11:g.109278889=Osman et al. 2020 Study with 914 indiv...

Other Reports

Kuwait

A household survey was carried out by Olusi et al. (2003) on 7,609 apparently healthy normal Kuwaiti Arabs aged 15 years and above to compute the prevalence of risk factors for coronary artery disease (CAD) amongst normal female subjects. The study consisted of 3,988 males, 3,621 females, and data collection focused on the prevalence of excessive weight, obesity, diabetes mellitus (hyperglycemia), dyslipidemia, current smoking, and physical inactivity. Blood samples were also gathered to determine glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoproteins A1 and B levels. Obesity was significantly prevalent among women (30%) than among men (17.5%) while diabetes mellitus, hypercholesterolemia, and physical inactivity was somewhat higher in women (21.8%, 36.6%, and 71.4%, respectively) than in men (17.7%, 30.2%, 50.6%, respectively). On the other hand, hypertriglyceridemia, low HDL-C, and the prevalence of smoking were higher in men (44.1%, 52.2%, and 31.7%, respectively) than in women (33.8%, 21.8%, and 1.4%, respectively). Olusi et al. (2003) concluded that female and male Kuwaitis have common risk factors for CAD and more awareness should be given to females to avoid CAD deaths amongst Kuwaitis.

Lebanon

Youhanna et al (2010) studied 4284 patients who underwent cardiac catheterization. The study found that a positive family hostoty of CAD in the presence of consangunity was strongly associated with a lower age of diagnosis of coronary artery disease. 

Saade et al. (2011) studied 2002 Lebanese subjects (608446.G.1) to identify an association between ten SNPs and susceptibility to CAD or MI. 1524 patients had coronary artery stenosis while 222 had a history of myocardial infarction. None of the ten SNPs showed association with CAD. 

Saudi Arabia

Abu-Amero et al. (2006a) conducted a study to analyze any potential correlation between the Gln27Glu polymorphism in the β2 adrenoceptor (ADRB2) gene and coronary artery disease (CAD) risk among Saudis.  Three groups of Saudi individuals were included in the study including 896 healthy individuals (BD group), 773 CAD patients (CAD group), and 528 individuals undergoing surgery for heart valvular disease who reported with chest pain (CON group).  The study revealed the presence of an association between the mutant (G) allele in the ADRB2 gene and an increased risk of CAD.  In another study, Abu-Amero et al. (2006b) examined the association between GSTT1 and GSTM1 deletion and coronary artery disease among smokers.  A total of 1054 CAD Saudi patients and 762 Saudi controls were genotyped.  The CAD individuals were 642 males with a mean age of 52 and 412 females with a mean age of 57.  The control group consisted of 464 males with a mean age of 53 and 298 females with a mean age of 55.  An association was found between the T null M null, T null M mild, and T mild M null genotypes with CAD independent of smoking interaction.  Also smoking, age, hypercholesterolemia and hypertriglyceridemia, diabetes mellitus, family history of CAD, hypertension, and obesity where all associated with CAD.

Elhawari et al., (2010) conducted a study among 1186 coronary artery disease patients, and 885 healthy individuals to evaluate the role of the MEF2A gene variants and their association with CAD in Saudi population.  Screening of the MEF2A gene showed several point mutations, and exon 11 was the most polymorphic locus with various substitution and insertion/deletion variants.  One of the SNPs in exon 11 (rs1059759 G>C) was found to be associated with CAD, while another (rs34851361) exhibited a weaker relationship.  Also one haplotype (1A-2G-3G-4A-5G-6A-7G-8A) with a frequency of 44.2% was associated with increased risk for CAD.  

Al-Jafari et al. (2012) carried out a study to determine the association between three LPL polymorphisms and CAD in the Saudi population.  The study recruited 120 CAD affected patients as well as 65 healthy ethnically matched controls.  The three variants detected using PCR-RFLP were LPL-HindIII, LPL-PvuII and LPL-Ser447Ter.  In the case of PvuII, the P+P+ genotype was seen in 41.7% of the CAD group and 38.5% of the control group.  For the Ser447Ter genotype, the C/C frequency was 83.3% in the CAD group and 87.7% in the control group.  Neither PvuII nor Ser447Ter polymorphisms showed any significant association with CAD.  With regards to the HindIII genotype, the frequency of H+H+ was 50.8% in the CAD group and 44.6% in the control group.  The odds ratio of H+H+ vs H-H- was 4.6 (1.57-13.2) with a p value less than 0.005.  Hence individuals with the H+H+ or H+H- genotype were at a much higher risk of developing CAD compared to individuals with H-H- genotype.  

Wakil et al. (2016) conducted a genome wide association study to identify susceptibility loci for Coronary Artery Disease (CAD) or Myocardial Infarction (MI) in the Saudi Arabian population. The study recruited 2668 CAD/MI affected patients and 3000 healthy controls based on their echocardiography and coronary angiography results.  All individuals were of Saudi Arabian origin.  Blood samples were retrieved from the patients and DNA was isolated.  Genotyping and statistical analysis were carried out to identify loci that had significant (p< 5x10-8) or suggestive (p< 1x10-5) associations with the disease.  Several genes were identified in this process. The rs10738607_G SNP, in the CDKN2A/B gene, showed the most statistically significant association with CAD (p=2.17E-08) followed by the rs12541758_T SNP in the TRPA1 gene (p=3.87E-07).  While CDKN2A/B has been implicated in MI/CAD studies in other ethnic groups, the authors noted that some of the variants discovered in this study differed from previous reports, suggesting ethnicity-related variation.  Other SNPs discovered to have an association with CAD include rs13082914_T in the KCNAB1 gene (p=3.64E-06), rs7421388_G in the PLCL1 gene (p=4.31E-06), rs9985766_G in the DCLK2 gene (p=3.36E-06), rs10981012_A in the C9orf84 gene (p=5.43E-06), rs1746049_C in the CXCL12 gene (p=2.44E-06) and the intergenic SNP rs17775862_T (p=5.33E-06).  Moreover, the study predicted the heritability of CAD to be approximately 33%.

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