scholarly journals An association between rs7635818 polymorphism located on chromosome 3p12.3 and the presence of abdominal aortic aneurysm

2021 ◽  
pp. 193-201
Author(s):  
M Rašiová ◽  
V Habalová ◽  
J Židzik ◽  
M Koščo ◽  
L Farkašová ◽  
...  

The association between gene variant rs7635818 located on chromosome 3p12.3 and abdominal aortic aneurysm (AAA) was not unambiguously determined by the results of genome-wide association studies. The aim of our study was to examine this possible association in the Slovak population, with respect to the presence and severity of AAA. A cross-sectional study was conducted between August 2016 and March 2020. The study included 329 participans, 166 AAA patients and a control group of 163 subjects without confirmed AAA with comparable distribution of genders. The anteroposterior diameter of the abdominal aorta was determined by duplex ultrasonography. AAA was defined as subrenal aortic diameter ≥ 30 mm. DNA samples were genotyped using real-time polymerase chain reaction and subsequent high-resolution melting analysis in presence of unlabelled probe. Genetic models studying the possible association were adjusted to age, sex, smoking, arterial hypertension, diabetes mellitus, creatinine and body mass index (BMI) in multivariate analysis. In the additive model, presence of each C-allele of rs7635818 polymorphism was associated with an almost 50 % increase in probability of developing AAA (OR 1.49; 95 % CI 1.06‒2.08; p=0.020). Compared to GG homozygotes, CC homozygotes had more than two times higher risk of developing AAA (OR 2.23; 95 % CI 1.14‒4.39; p=0.020). The risk of AAA was also in the recessive model higher for CC homozygotes compared to G-allele carriers (GC/GG) (OR 1.79; 95 %CI 1.01‒3.19; p=0.047). The abdominal aortic diameter in CC homozygotes of the rs7635818 polymorphism was 7.66 mm greater compared to GG homozygotes (42.5±22.0 mm vs 34.8±21.3 mm; p=0.022) and 5.88 mm greater compared to G-allele carriers (GC/GG) (42.5±22.0 mm vs 36.6±21.0 mm; p=0.04) in univariate analysis. C-allele variant in rs7635818 G>C polymorphism is associated with a higher probability of developing AAA in the Slovak population.

2012 ◽  
Vol 166 (2) ◽  
pp. 191-197 ◽  
Author(s):  
Bu B Yeap ◽  
S A Paul Chubb ◽  
Kieran A McCaul ◽  
Leon Flicker ◽  
Ken K Y Ho ◽  
...  

ObjectiveAbdominal aortic aneurysm (AAA) is most prevalent in older men. GH secretion declines with age resulting in reduced IGF1 levels. IGF1 and its binding proteins (IGFBPs) are expressed in vasculature, and lower IGF1 levels have been associated with cardiovascular risk factors and disease. However, the relationship of the IGF1 system with aortic dilation and AAA is unclear. We tested the hypothesis that circulating IGF1 and IGFBPs are associated with AAA and aortic diameter in older men.DesignA cross-sectional analysis involving 3981 community-dwelling men aged 70–89 years was performed.MethodsAbdominal aortic diameter was measured by ultrasound. Plasma total IGF1, IGFBP1 and IGFBP3 were measured by immunoassays.ResultsAfter adjustment for age, body mass index, waist:hip ratio, smoking, hypertension, dyslipidemia, diabetes, coronary heart disease and serum creatinine, a higher IGF1 level was associated with AAA (odds ratio (OR)/1 s.d. increase 1.18, 95% confidence interval (CI) 1.05–1.33, P=0.006), as was the ratio of IGF1/IGFBP3 (OR=1.22, 95% CI 1.10–1.35, P<0.001). Highest IGF1 concentrations compared with lowest quintile were significantly associated with AAA (quintile (Q) 5 vs Q1: OR=1.80, 95% CI 1.20–2.70, P=0.004) as were IGF1/IGFBP3 ratios (Q5 vs Q1: OR=2.52, 95% CI 1.59–4.02, P<0.001). IGF1 and IGFBP1 were independently associated with aortic diameter (β=0.200, 95% CI 0.043–0.357, P=0.012 and β=0.274, 95% CI 0.098–0.449, P=0.002 respectively).ConclusionsIn older men, higher IGF1 and an increased ratio of IGF1/IGFBP3 are associated with AAA, while IGFBP1 is independently associated with increased aortic diameter. Components of the IGF1 system may contribute to, or be a marker for, aortic dilation in ageing men.


2017 ◽  
Vol 120 (2) ◽  
pp. 341-353 ◽  
Author(s):  
Gregory T. Jones ◽  
Gerard Tromp ◽  
Helena Kuivaniemi ◽  
Solveig Gretarsdottir ◽  
Annette F. Baas ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-22
Author(s):  
Abulaihaiti Maitiseyiti ◽  
Hongbo Ci ◽  
Qingbo Fang ◽  
Sheng Guan ◽  
Alimujiang Shawuti ◽  
...  

Objective. Long noncoding RNAs (lncRNAs) have emerged as critical molecular regulators in various diseases. However, the potential regulatory role of lncRNAs in the pathogenesis of abdominal aortic aneurysm (AAA) remains elusive. The aim of this study was to identify crucial lncRNAs associated with human AAA by comparing the lncRNA and mRNA expression profiles of patients with AAA with those of control individuals. Materials and Methods. The expression profiles of lncRNAs and mRNAs were analyzed in five dilated aortic samples from AAA patients and three normal aortic samples from control individuals using microarray technology. Functional annotation of the screened lncRNAs based on the differentially expressed genes was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results. Microarray results revealed 2046 lncRNAs and 1363 mRNAs. Functional enrichment analysis showed that the mRNAs significantly associated with AAA were enriched in the NOD-like receptor (NLR) and nuclear factor kappa-B (NF-κB) signaling pathways and in cell adhesion molecules (CAMs), which are closely associated with pathophysiological changes in AAA. The lncRNAs identified using microarray analysis were further validated using quantitative real-time polymerase chain reaction (qRT-PCR) analysis with 12 versus 11 aortic samples. Finally, three key lncRNAs (ENST00000566954, ENST00000580897, and T181556) were confirmed using strict validation. A coding-noncoding coexpression (CNC) network and a competing endogenous RNA (ceRNA) network were constructed to determine the interaction among the lncRNAs, microRNAs, and mRNAs based on the confirmed lncRNAs. Conclusions. Our microarray profiling analysis and validation of significantly expressed lncRNAs between patients with AAA and control group individuals may provide new diagnostic biomarkers for AAA. The underlying regulatory mechanisms of the confirmed lncRNAs in AAA pathogenesis need to be determined using in vitro and in vivo experiments.


Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Weihong Tang ◽  
Alvaro Alonso ◽  
Pamela L Lutsey ◽  
Frank A Lederle ◽  
Lu Yao ◽  
...  

Introduction: Abdominal aortic aneurysm (AAA) is an important manifestation of vascular disease in older age and rupture of an AAA is a life threatening condition. Traditional atherosclerotic disease risk factors, particularly male sex, smoking and hypertension, are known to contribute to the etiology of AAA. However, epidemiologic studies of AAA have often been cross-sectional, and few have employed a prospective cohort design, especially with long follow-up. The objective of this study was to prospectively assess the association between atherosclerotic disease risk factors and hospitalized AAA in 15,722 participants (68% whites) of the ARIC study, a large, community-based cohort. Methods: Risk factors were measured at baseline at 45-64 year of age. Clinical AAAs were ascertained through hospital discharge diagnoses or death certificates. Over 15 years of follow-up, a total of 265 AAAs (85.3% whites) were identified, including repair procedures, AAA rupture or dissection, and incidental detection. Multivariable Cox proportional hazard models were used to estimate the association of risk factors with the risk of future AAA. Results: Consistent with the literature from prospective studies, we identified age, male gender, white race, smoking, height, total and HDL cholesterols, triglycerides, white blood cell count, and hypertension as risk factors for AAA (Table). In addition, LDL-C, fibrinogen, and peripheral artery disease that were previously reported only in cross-sectional case-control studies were also strongly associated with AAA (Table). Body mass index, diabetes, and alcohol consumption were not associated with AAA occurrence. Conclusions: Several lifestyle and clinical variables measured in middle-age were strong risk factors for future AAA during a long follow-up.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Kunihiro Matsushita

Introduction: Diabetes mellitus is known to be related to lower risk of abdominal aortic aneurysm (AAA). However, the full spectrum of glycemic status including prediabetes and the duration of diabetes have not been extensively investigated in the context of AAA risk. Methods: We prospectively studied incident AAA (defined using outpatient records, hospitalization discharge, or death certificate) according to the baseline glycemic status defined using physician diagnosed diabetes, self-reported anti-diabetic medication use and glucose or hemoglobin A1c (diabetes, pre-diabetes, vs. normal glycemia) in 13,116 participants (1990-1992) and the time-varying exposure of duration of incident diabetes in 11,675 participants (1987-1989) using Cox models. We cross-sectionally explored ultrasound-based abdominal aortic diameter by glycemic status and cumulative duration of diabetes in 4,710 participants (2011-2013) using linear regression models. Results: There were 489 incident AAA cases during a median follow-up of ~20 years. Diabetes but not pre-diabetes (vs. normal glycemia) at baseline was independently associated with lower risk of AAA (HR: 0.71 [95%CI 0.51 - 0.99]). The association was largely driven by long-standing diabetes (≥10 years duration: HR: 0.58 [95%CI 0.38 - 0.87]). Longer duration of diabetes was associated with lower risk of AAA (Figure 1A), with 30-50% lower risk in 8 years after incident diabetes diagnosis, as well as smaller aortic diameter measured cross-sectionally (Figure 1B) compared to non-diabetes. Pre-diabetes consistently showed relatively greater diameter (e.g., +0.26 mm [-0.03, +0.54]). Conclusions: Diabetes (but not prediabetes) and its longer duration were independently associated with lower risk of AAA and smaller aortic diameter. Our findings suggest that the cumulative effects of hyperglycemia may play a role in the counterintuitively lower AAA risk. Reduced aortic diameter might be a structural mechanism of decreased AAA risk in diabetes. Figure 1A. Adjusted hazard ratio of incident AAA according to the duration of diabetes among incident cases as a time-varying exposure; Figure 1B. Adjusted difference in maximum diameter (mm) for diabetes vs. non-diabetes by cumulative duration of diabetes. Both models adjusted for age, sex, race, education, BMI, height, total cholesterol, HDL cholesterol, systolic blood pressure, diastolic blood pressure, anti-hypertensive medication, cholesterol-lowering medication, cigarette smoking pack-years, alcohol drinking, eGFR, prevalent peripheral artery disease, prevalent coronary heart disease, and prevalent stroke (time-varying covariates for Figure 1A and baseline covariates for Figure 1B).


BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e027291
Author(s):  
Wing Cheuk Chan ◽  
Dean Papaconstantinou ◽  
Doone Winnard ◽  
Gary Jackson

ObjectivesTo describe the proportions of people dying from abdominal aortic aneurysm (AAA) who might have benefited from a formal screening programme for AAA.DesignRetrospective cross-sectional review of deaths.Setting and study populationsAll AAA deaths registered in New Zealand from 2010 to 2014 in the absence of a national AAA screening programme.Main outcome measuresKnown history of AAA prior to the acute event leading to AAA death, prognosis limiting comorbidities, history of prior abdominal imaging and a validated multimorbidity measure (M3-index scores).Results1094 AAA deaths were registered in the 5 years between 2010 and 2014 in New Zealand. Prior to the acute AAA event resulting in death, 31.3% of the cohort had a known AAA diagnosis, and 10.9% had a previous AAA procedure. On average, the AAA diagnosis was known 3.7 years prior to death. At least 77% of the people dying from AAA also had one or more other prognosis limiting diagnosis. The hazard of 1-year mortality associated with the non-AAA related comorbidities for the AAA cohort aged 65 or above were 1.5–2.6 times higher than to the age matched general population based on M3-index scores. In 2014, overall AAA deaths accounted for only 0.7% of total deaths, and 1.0% of deaths among men aged 65 or above in New Zealand. At most, 20% of people dying from AAA in New Zealand between 2010 and 2014 might have had the potential to derive full benefit from a screening programme. About 51% of cases would have derived no or very limited benefit from a screening programme.ConclusionFalling AAA mortality, and high prevalence of competing comorbidities and/or prior AAA diagnosis and procedure raises the question about the likely value of a national AAA screening programme in a country such as New Zealand.


2019 ◽  
Vol 7 ◽  
pp. 205031211983350 ◽  
Author(s):  
Kristian Smidfelt ◽  
Joakim Nordanstig ◽  
Urban Wingren ◽  
Göran Bergström ◽  
Marcus Langenskiöld

Objective: To investigate whether a strategy of treatment with a primarily open abdomen improves outcome in terms of mortality and major complications in patients treated with open repair for a ruptured abdominal aortic aneurysm compared to a strategy of primary closure of the abdomen. Design: Retrospective cohort study. Methods: Patients treated with a primarily open abdomen at a centre where this strategy was routine in most ruptured abdominal aortic aneurysm patients were compared to a propensity score–matched control group of patients who had the abdomen closed at the end of the primary operation in a majority of the cases. Results: In total, 79 patients treated with a primarily open abdomen after open repair for ruptured abdominal aortic aneurysm at Sahlgrenska University Hospital were compared to a propensity score–matched control group of 148 patients. The abdomen was closed at the end of the procedure in 108 (73%) of the control patients. There was no difference in 30-day mortality between patients treated with a primarily open abdomen at Sahlgrenska University Hospital and the controls, 21 (26.6%) versus 49 (33.1%), p = 0.37. The adjusted odds ratio for mortality at 30 days was 0.66 (95% confidence interval: 0.35–1.25) in patients treated with a primarily open abdomen at Sahlgrenska University Hospital compared to the controls. No difference was observed between the groups regarding 90-day mortality, postoperative renal failure requiring renal replacement therapy, postoperative intestinal ischaemia necessitating bowel resection or postoperative bleeding requiring reoperation. Conclusions: The study did not show any survival advantage or difference in major complications between patients treated with a primarily open abdomen after open repair for ruptured abdominal aortic aneurysm and propensity-matched controls where the abdomen was primarily closed in a majority of the cases.


2020 ◽  
Vol 91 (11) ◽  
pp. 1453-1464
Author(s):  
Leila Salhi ◽  
Natzi Sakalihasan ◽  
Ambre Gau Okroglic ◽  
Nicos Labropoulos ◽  
Laurence Seidel ◽  
...  

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