Rationale
Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA.
Objective
To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS).
Methods and Results
Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches we observed no new associations between the lead AAA SNPs and coronary artery disease, blood pressure, lipids or diabetes. Network analyses identified ERG, IL6R and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9.
Conclusions
The 4 new risk loci for AAA appear to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
There is a strong body of circumstantial evidence which implicates genetics in the aetiology and pathology of varicose veins and venous ulcer disease. The aim of this review is to consider the current knowledge of the genetic associations and the ways in which new genetic technologies may be applied to advancing our understanding of the cause and progression of these venous diseases. A number of publications have used a candidate gene approach to identify genes implicated in venous disease. Although these studies have opened up important new insights, there has been a general failure to replicate results in an independent cohort of patients. With our limited knowledge of the biological pathways involved in the pathogenesis of venous disease we are not in a strong position to formulate truly erudite a priori candidate gene hypothesis-directed studies. A genome-wide association study should therefore be considered to help further our understanding of the genetic basis of venous disease. Due to the large sample sizes required for discovery and validation, using the new generations of molecular technologies, it will be necessary to form collaborating groups in order to successfully advance the field of venous disease genetics.
Renal patients have a high rate of complications after colorectal surgery, and emergency surgery has a significant risk of anastomotic leak. Primary anastomosis should be avoided in all patients undergoing emergency intestinal resections. Subsequent surgery to restore intestinal continuity is possible in 90 percent of patients with far fewer complications.
WHAT THIS PAPER ADDS AAA is widely reported as having a significantly higher prevalence in males. This study adds to a body of evidence suggesting that sex differences in AAA prevalence are largely an artefact of the application of a single (male derived) absolute size threshold. Any discussion on the retention or future development of AAA screening programmes must use appropriate sex specific prevalence rates in order to provide a balanced and equitable consideration.Objective: Recently, the prevalence of abdominal aortic aneurysm (AAA) using screening strategies based on elevated cardiovascular disease (CVD) risk was reported. AAA was defined as a diameter !30 mm, with prevalence of 6.1% and 1.8% in men and women respectively, consistent with the widely reported AAA predominant prevalence in males. Given the obvious differences in body size between sexes this study aimed to re-evaluate the expanded CVD risk based AAA screening dataset to determine the effect of body size on sex specific AAA prevalence. Methods: Absolute (26 and 30 mm) and relative (aortic size index [ASI] equals the maximum infrarenal aorta diameter (cm) divided by body surface area (m 2 ), ASI ! 1.5) thresholds were used to assess targeted AAA screening groups (n ¼ 4115) and compared with a self reported healthy elderly control group (n ¼ 800). Results: Male AAA prevalence was the same using either the 30 mm or ASI !1.5 aneurysm definitions (5.7%). In females, AAA prevalence was significantly different between the 30 mm (2.4%) and ASI ! 1.5 (4.5%) or the 26 mm (4.4%) thresholds. Conclusion: The results suggest the purported male predominance in AAA prevalence is primarily an artefact of body size differences. When aortic size is adjusted for body surface area there is only a modest sex difference in AAA prevalence. This observation has potential implications in the context of the ongoing discussion regarding AAA screening in women.
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