News | January 05, 2010

Hereditary Factors Contribute to Aneurysms in Twins

January 5, 2010 - Researchers found robust epidemiological evidence that hereditary factors contribute to aneurysm formation in twins, in a new study published in the January issue of the Journal of Vascular Surgery. According to the authors, the study emphasizes the importance of evaluating family history in patients with AAA and supports ultrasound scan screening of unaffected siblings.

Researchers in Sweden reviewed the data of 172,890 twins born in that country since 1886 and found 265 twins who had developed abdominal aortic aneurysms (AAAs). These individuals ranged from 48 to 94 years of age; 81 percent were male. Carl Magnus Wahlgren, M.D., Ph.D., from the department of vascular surgery at Karolinska University Hospital in Stockholm, said that this was the largest AAA population-based twin study to date.

"There were seven sets of identical (monozygotic) as well as five sets of fraternal (dizygotic) concordant pairs," said Dr. Wahlgren. "Concordance rates represent the probability of developing AAA for an individual with an affected twin. The identical pairs had a 24 percent probability that an identical twin of a person with AAA would get the disease. Their risk was 71 times higher than that of the identical twin of a person without AAA. The probability rate for the concordant fraternal twins was 4.8 percent. In contrast, there were 44 identical and 197 fraternal discordant pairs in the AAA group."

Researchers also reviewed the data for twins with AAA ages 55 years and older, then possibly excluding genetic connective tissue disorders such as Ehler-Danlos and Marfan syndrome, the odds ratio still was significantly higher for identical as opposed to fraternal twins. Heritability of 70 percent of the total trait variance was estimated and the remaining variance was explained by non-shared environmental factors with no support for a role of shared environmental influences.

"Our twin model provides a powerful means of examining the total genetic contribution to a given disease especially a complex trait such as AAA, and phenotypes (genetic makeup and environmental influences) can be defined to maximize chances of successful gene mapping," said Dr. Wahlgren. "Unlike family or sibling studies, potential confounders such as the variability of disease prevalence with age are removed. This model relies on important assumptions, including random mating, no interaction between genes and environment and equivalent environments for identical and fraternal twins."

The study had only one female concordant twin pair with AAA. Researchers said they could not draw any conclusions about a possible stronger heritability in men or women. They noted that in other regions the proportions of type of effects could differ because of environmental factors; also in the cases of aneurysmal disease with several genetic and environmental factors, the liability model assumes that the disease will occur when there are enough contributory factors to push the individual's liability above the threshold.

"The data can improve the information given to first-degree relatives of patients with AAA regarding the risk," said Dr. Wahlgren. "However, many questions in the genetics of familial AAA remain unanswered. The understanding about how risk factors and genotype contribute to AAA development is important for patient selection, screening and more aggressive treatment."

For more information: www.vascularweb.org

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