Genetic linkage of candidate genes in families with abdominal aortic aneurysms?

Abstract

to examine possible involvement of several candidate genes in the aetiology of familial abdominal aortic aneurysm (AAA). after reviewing the literature on the genetics of familial AAA, betaine homocysteine methyltransferase (BHMT), collagen type Ialpha2 (COL1A2) and cathepsin H (CTSH), were selected as potential candidate genes, which influence structure, strength, elasticity and mechanical resistance of the aortic wall. forty-eight families with 110 family members and AAA were included in the affected sib-pair analysis. One large family of three generations was analysed separately because in this family also other clinical symptoms were involved. genetic linkage analysis was performed with DNA markers in the region of BHMT, COL1A2 and CTSH. In the overall sib-pair analysis, the LOD scores for BHMT, COL1A2 and CTSH were 0.7, 0.2 and -0.7, whereas in the large family these numbers were -0.6, -2.2 and -2.7, respectively. none of the candidate genes selected showed a suggestive linkage with AAA. Exclusion of the COL1A2 and CTSH genes was possible in the large family that was analysed separately.