Background-Abdominal aortic aneurysm (AAA) is a relatively common disease, with 1% to 2% of the population harboring aneurysms. Genetic risk factors are likely to contribute to the development of AAAs, although no such risk factors have been identified. Methods and Results-We performed a whole-genome scan of AAA using affected-relative-pair (ARP) linkage analysis that includes covariates to allow for genetic heterogeneity. We found strong evidence of linkage (logarithm of odds [LOD] scoreϭ4.64) to a region near marker D19S433 at 51.88 centimorgans (cM) on chromosome 19 with 36 families (75 ARPs) when including sex and the number of affected first-degree relatives of the proband (N aff ) as covariates. We then genotyped 83 additional families for the same markers and typed additional markers for all families and obtained a LOD score of 4.75 (Pϭ0.00014) with sex, N aff , and their interaction as covariates near marker D19S416 (58.69 cM).We also identified a region on chromosome 4 with a LOD score of 3.73 (Pϭ0.0012) near marker D4S1644 using the same covariate model as for chromosome 19. Conclusions-Our results provide evidence for genetic heterogeneity and the presence of susceptibility loci for AAA on chromosomes 19q13 and 4q31.

Abdominal aortic aneurysms (AAAs) are an important cardiovascular disease, but the genetic and environmental risk factors, which contribute to individual's risk to develop an aneurysm, are poorly understood. Histologically, AAAs are characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. We hypothesized that genes involved in these events could harbor changes that make individuals more susceptible to developing aneurysms. This study identified significant genetic associations between DNA sequence changes in tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and elastin (ELN) genes, and AAA. The results will require confirmation using an independent set of samples. After replication it is possible that these sequence changes in combination with other risk factors could be used in the future to identify individuals who are at increased risk for developing an AAA.

No abstract

There was a significant difference between the siblings of the AAA patients and those of the spouses both in the frequency of AAA detected by ultrasonography screening and in the overall prevalence of AAA. The overall prevalence of AAA in the siblings of AAA patients was about eight times that observed among the siblings of their spouses (19.2% vs 2.3%). These findings confirmed previous reports on high prevalence of AAA among siblings of AAA patients and emphasized the importance of an ultrasonography screening program for siblings of AAA patients.

No abstract

No abstract

Hypertrophic cardiomyopathy (HCM) is a rare cardiac complication in patients with Klinefelter syndrome. We report the case of a 67-year-old Japanese man with Klinefelter syndrome, HCM, sick sinus syndrome, and coronary arteriovenous fistula, in whom the 47XXY/46XY mosaic pattern was revealed by chromosomal study. Echocardiography revealed HCM with an interventricular septum thickness of 17 mm and a left ventricular posterior wall thickness of 10 mm. Sick sinus syndrome type III was diagnosed by paroxysmal atrial fibrillation (longest sinus arrest 9.0 sec) on 24-h Holter ECG recording. Coronary arteriovenous fistula was detected from the left anterior descending artery to the right ventricle by coronary arteriography. To our knowledge, this is the first case report of Klinefelter syndrome with HCM. As there have been a few reports of patients with Klinefelter syndrome in association with skeletal muscular diseases such as Becker-type muscular dystrophy or myotonic dystrophy, the gene mutation that causes Klinefelter syndrome may occur in the cardiac muscle. HCM may represent another variable expression of this chromosomal abnormality.

Background: Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with HLA polymorphisms.