scholarly journals Mutational Spectrum of LDLR and PCSK9 Genes Identified in Iranian Patients With Premature Coronary Artery Disease and Familial Hypercholesterolemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Arman Moradi ◽  
Majid Maleki ◽  
Zahra Ghaemmaghami ◽  
Zahra Khajali ◽  
Feridoun Noohi ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Familial Hypercholesterolemia ◽  
Genetic Disorder ◽  
Premature Coronary Artery Disease ◽  
Double Mutation ◽  
The Family ◽  
Premature Cad ◽  
Artery Disease ◽  
Iranian Patients

Familial hypercholesterolemia (FH) is a common, yet underdiagnosed, genetic disorder characterized by lifelong elevated low-density lipoprotein cholesterol levels, which can increase the risk of early-onset coronary artery disease (CAD). In the present study, we screened the nucleotide variations of the LDLR and PCSK9 genes, as well as a part of the APOB gene, in Iranian patients with FH and premature CAD to find the genetic cause of the disorder. Fifteen unrelated individuals with a clinical diagnosis of FH and premature CAD were recruited. Direct DNA sequencing was applied to screen the whole coding exons and exon–intron boundaries of the LDLR and PCSK9 genes and the main parts of their introns, together with exon 26 of the APOB gene. The pathogenicity of the identified mutations was investigated via either segregation analyses in the family or in silico predictive software. Six different point mutations (p.Cys148Tyr, p.Cys216Tyr, p.Cys302Trp, p.Cys338Trp, p.Leu479Gln, and p.G593Afs∗72) in LDLR and a double mutation (p.Asp172His and p.Ala53Val) in both LDLR and PCSK9 genes were identified in seven families with clinically diagnosed FH (43%), whereas no pathogenic mutations were found in eight families with clinically diagnosed FH. This study is the first to identify 1 pathogenic mutation in the LDLR gene (c.1014C > G [p.Cys338Trp]) and to cosegregate it from the affected individual in the family. No mutations were found in the APOB gene, whereas several silent mutations/polymorphisms were identified in the LDLR and PCSK9 genes. Genetic testing and reports on nucleotide alterations in the Iranian population are still limited. Our findings not only further confirm the significant role of FH in the incidence of premature CAD but also enlarge the spectrum of LDLR and PCSK9 variations and exhibit the heterogeneity of FH in Iranians. In patients with no mutation in the examined genes, the disease could be begotten either by a polygenic cause or by gene defects occurring in other related genes and regions not targeted in this study.

scholarly journals A case of familial hypercholesterolemia with premature coronary artery disease

Heart India ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 156
Author(s):  
DigvijayDeeliprao Nalawade ◽  
JaywantM Nawale ◽  
AjayS Chaurasia ◽  
Dhirendra Tiwari
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Familial Hypercholesterolemia ◽  
Premature Coronary Artery Disease ◽  
Artery Disease

Abstract 18995: Statins in Familial Hypercholesterolemia - Effects on Coronary Artery Disease and All-cause Mortality

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Joost Besseling ◽  
Gerard K Hovingh ◽  
John J Kastelein ◽  
Barbara A Hutten
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Familial Hypercholesterolemia ◽  
Lipid Lowering ◽  
Premature Coronary Artery Disease ◽  
Lipid Lowering Therapy ◽  
Time Varying ◽  
All Cause Mortality ◽  
Artery Disease

Introduction: Heterozygous familial hypercholesterolemia (heFH) is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk for premature coronary artery disease (CAD) and death. Reduction of CAD and mortality by statins has not been properly quantified in heFH. The aim of the current study is to determine the effect of statins on CAD and mortality in heFH. Methods: All adult heFH patients identified by the Dutch FH screening program between 1994 and 2014 and registered in the PHARMO Database Network were eligible. Of these patients we obtained hospital, pharmacy (in- and outpatient), and mortality records in the period between 1995 and 2015. The effect of statins (time-varying) on CAD and all-cause mortality was determined using a Cox proportional hazard model, while correcting for the use of other lipid-lowering therapy, thrombocyte aggregation inhibitors, antihypertensive and antidiabetic medication (all time-varying). Furthermore, we used inverse probability for treatment weighting (IPTW) to account for differences between statin-treated and untreated patients regarding history of CAD before follow-up, age at start of follow-up and age of screening, as well as body mass index, LDL-C and triglycerides. Results: Of the 25,479 identified heFH patients, 11,021 gave informed consent to obtain their medical records, of whom 2,447 could be retrieved. We excluded 766 patients younger than 18. The remaining 1,681 heFH patients comprised our study population and these had very similar characteristics as compared to the 23,798 excluded FH patients, e.g. mean (SD) LDL-C levels were 214 (74) vs. 203 (77) mg/dL. Among 1,151 statin users, there were 133 CAD events and 15 deaths during 10,115 statin treated person-years, compared to 17 CAD events and 9 deaths during 4,965 person-years in 530 never statin users (combined rate: 14.6 vs. 5.2, respectively, p<0.001). After applying IPTW to account for indication bias and correcting for use of other medications, the hazard ratio of statin use for CAD and all-cause mortality was 0.61 (0.40 - 0.93). Conclusions: In heFH patients, statins lower the risk for CAD and mortality by 39%.

scholarly journals The frequency of anti-phospholipid antibody syndrome in patients with premature coronary artery disease

2018 ◽  
Vol 10 (4) ◽  
pp. 227-230
Author(s):  
Gholamhossein Alishiri ◽  
Maryam Moshkani Farahani ◽  
Ali Sadr ◽  
Mahmood Salesi ◽  
Mostafa Rahemi ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Young Adults ◽  
Coronary Artery ◽  
Cross Sectional Study ◽  
Premature Coronary Artery Disease ◽  
Sectional Study ◽  
Cross Sectional ◽  
The World ◽  
Premature Cad ◽  
Artery Disease

Introduction: Coronary Artery Disease (CAD) is known as the major cause of morbidity and mortality in the world with a growing trend, especially in some developing countries. CAD commonly observed in elderly cases, however; recently it is usually found in young adults. In this study, we aimed to evaluate the prevalence of anti-phospholipid antibody syndrome (APS) in patients with premature CAD. Methods: The cross-sectional study was conducted in Baqiyatallah hospital from April 2012 to April 2016. Patients with premature CAD were included in the study. The data regarding the laboratory tests, echocardiography, and angiography were obtained from all cases. Results: Overall 133 eligible patients were included in the study. In the first set of the laboratory test, 18 patients were recognized to have APS (13.53%). The second confirmatory APA test was showing 3 of 18 patients were considered to have APS (2.25%). Conclusion: The results showed there is an association between the risk of developing Premature CAD and APS could potentially. The APS may have significant effects on the risk of coronary heart disease, especially in young adults.

scholarly journals Raet1e Polymorphisms Are Associated with Increased Risk of Developing Premature Coronary Artery Disease and with Some Cardiometabolic Parameters: The GEA Mexican Study

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Rosalinda Posadas-Sánchez ◽  
Bladimir Roque-Ramírez ◽  
José Manuel Rodríguez-Pérez ◽  
Nonanzit Pérez-Hernández ◽  
José Manuel Fragoso ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Premature Coronary Artery Disease ◽  
Functional Effect ◽  
Increased Risk ◽  
Family Medical History ◽  
History Of ◽  
Premature Cad ◽  
Artery Disease ◽  
First Time

In an animal model, new evidence has been reported supporting the role of raet1e as an atherosclerosis-associated gene. Our objective was to establish if raet1e polymorphisms are associated with the risk of developing premature coronary artery disease (CAD) or with the presence of cardiometabolic parameters. After an informatic analysis, five polymorphisms were chosen and determined in 1158 patients with premature CAD and 1104 controls using 5′ exonuclease TaqMan genotyping assays. Standardized questionnaires were applied to all participants to obtain family medical history, demographic information, history of nutritional habits, physical activity, alcohol consumption, and pharmacological treatment. The functional effect of the rs7756850 polymorphism was analyzed by luciferase assays. Under different models, adjusted by age, gender, body mass index, current smoking, and type 2 diabetes mellitus, the rs6925151 (OR=1.250, pheterozygote=0.026; OR=1.268, pcodominant1=0.034), rs9371533 (OR=1.255, pheterozygote=0.024), rs7756850 (OR=1.274, pheterozygote=0.016; OR=1.294, pcodominant1=0.031), and rs9383921 (OR=1.232, pheterozygote=0.037) polymorphisms were associated with increased risk of premature CAD. When compared to the rs7756850 G allele, the C allele showed a decreased luciferase activity. In premature CAD patients, associations with low levels of adiponectin, with a high presence of hypertension, and with high levels of gamma-glutamyltransferase and total cholesterol were observed. In healthy controls, associations with a decrease in LDL pattern B, aspartate aminotransaminase, and hypo-α-lipoproteinemia were detected. An association of the raet1e polymorphisms with an increased risk of developing premature CAD and with cardiometabolic parameters has been shown for the first time. In addition, the functional effect of the rs7756850 polymorphism was defined.

scholarly journals Coronary plaque tissue characterization in patients with premature coronary artery disease

2020 ◽  
Vol 36 (6) ◽  
pp. 1003-1011
Author(s):  
Jianchang Xie ◽  
Jie Qi ◽  
Hengyi Mao ◽  
Ningfu Wang ◽  
Xianhua Ye ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Plaque ◽  
Plaque Burden ◽  
Premature Coronary Artery Disease ◽  
Coronary Risk Factors ◽  
Matching Procedure ◽  
Premature Cad ◽  
Artery Disease

Abstract Premature coronary artery disease (CAD) studies rarely involve coronary plaque characterization. We characterize coronary plaque tissue by radiofrequency intravascular ultrasound (IVUS) in patients with premature CAD. From July 2015 to December 2017, 220 patients from the Department of Cardiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine with first occurrence of angina or myocardial infarction within 3 months were enrolled. Patients with premature CAD (n = 47, males aged < 55 years, and females aged < 65 years) or later CAD (n = 155) were retrospectively compared for cardiovascular risk factors, laboratory examination findings, coronary angiography data, gray-scale IVUS, and iMap-IVUS. The mean age was 53.53 ± 7.24 vs. 70.48 ± 8.74 years (p < 0.001). The groups were similar for traditional coronary risk factors except homocysteine (18.60 ± 5.15 vs. 17.08 ± 4.27 µmol/L, p = 0.043). After matching for baseline characteristics, LDL cholesterol (LDL-C) was higher for premature CAD than later CAD (2.50 ± 0.96 vs. 2.17 ± 0.80 mmol/L, p = 0.019). Before the matching procedure, the premature CAD group had shorter target lesion length [18.50 (12.60–32.00) vs. 27.90 (18.70–37.40) mm, p = 0.002], less plaque volume [175.59 (96.60–240.50) vs. 214.73 (139.74–330.00) mm3, p = 0.013] than the later CAD group. After the matching procedure, the premature CAD group appeared to be less plaque burden (72.69 ± 9.99 vs. 74.85 ± 9.80%, p = 0.005), and positive remodeling (1.03 ± 0.12 vs. 0.94 ± 0.18, p = 0.034), and lower high risk feature incidence (p = 0.006) than the later CAD group. At the plaque’s minimum lumen, premature CAD had more fibrotic (p < 0.001), less necrotic (p = 0.001) and less calcified areas (p = 0.012). Coronary plaque tissue was more fibrotic with less necrotic and calcified components in premature than in later CAD, and the range and degree of atherosclerosis were significantly lower.

scholarly journals Fibrinogen and a Triad of Thrombosis, Inflammation, and the Renin-Angiotensin System in Premature Coronary Artery Disease in Women: A New Insight into Sex-Related Differences in the Pathogenesis of the Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1036
Author(s):  
Karolina E. Kryczka ◽  
Mariusz Kruk ◽  
Marcin Demkow ◽  
Barbara Lubiszewska
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Young Women ◽  
Plaque Formation ◽  
Tissue Type ◽  
Premature Coronary Artery Disease ◽  
Renin Angiotensin ◽  
Premature Cad ◽  
Artery Disease

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in women worldwide. Its social impact in the case of premature CAD is particularly devastating. Many differences in the presentation of the disease in women as compared to men, including atypical symptoms, microvascular involvement, and differences in pathology of plaque formation or progression, make CAD diagnosis in women a challenge. The contribution of different risk factors, such as smoking, diabetes, hyperlipidemia, or obesity, may vary between women and men. Certain pathological pathways may have different sex-related magnitudes on CAD formation and progression. In spite of the already known differences, we lack sufficiently powered studies, both clinical and experimental, that assess the multipathogenic differences in CAD formation and progression related to sex in different age periods. A growing quantity of data that are presented in this article suggest that thrombosis with fibrinogen is of more concern in the case of premature CAD in women than are other coagulation factors, such as factors VII and VIII, tissue-type plasminogen activator, and plasminogen inhibitor-1. The rise in fibrinogen levels in inflammation is mainly affected by interleukin-6 (IL-6). The renin–angiotensin (RA) system affects the inflammatory process by increasing the IL-6 level. Unlike in men, in young women, the hypertensive arm of the RA system is naturally downregulated by estrogens. At the same time, estrogens promote the fibrinolytic path of the RA system. In young women, the promoted fibrinolytic process upregulates IL-6 release from leukocytes via fibrin degradation products. Moreover, fibrinogen, whose higher levels are observed in women, increases IL-6 synthesis and exacerbates inflammation, contributing to CAD. Therefore, the synergistic interplay between thrombosis, inflammation, and the RA system appears to have a more significant influence on the underlying CAD atherosclerotic plaque formation in young women than in men. This issue is further discussed in this review. Fibrinogen is the biomolecule that is central to these three pathways. In this review, fibrinogen is shown as the biomolecule that possesses a different impact on CAD formation, progression, and destabilization in women to that observed in men, being more pathogenic in women at the early stages of the disease than in men. Fibrinogen is a three-chain glycoprotein involved in thrombosis. Although the role of thrombosis is of great magnitude in acute coronary events, fibrinogen also induces atherosclerosis formation by accumulating in the arterial wall and enabling low-density lipoprotein cholesterol aggregation. Its level rises during inflammation and is associated with most cardiovascular risk factors, particularly smoking and diabetes. It was noted that fibrinogen levels were higher in women than in men as well as in the case of premature CAD in women. The causes of this phenomenon are not well understood. The higher fibrinogen levels were found to be associated with a greater extent of coronary atherosclerosis in women with CAD but not in men. Moreover, the lysability of a fibrin clot, which is dependent on fibrinogen properties, was reduced in women with subclinical CAD compared to men at the same stage of the disease, as well as in comparison to women without coronary artery atherosclerosis. These findings suggest that the magnitude of the pathological pathways contributing to premature CAD differs in women and men, and they are discussed in this review. While many gaps in both experimental and clinical studies on sex-related differences in premature CAD exist, further studies on pathological pathways are needed.

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