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

Objectives: to examine possible involvement of several candidate genes in the aetiology of familial abdominal aortic aneurysm (AAA). Design: 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. Materials: 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. Methods: genetic linkage analysis was performed with DNA markers in the region of BHMT, COL1A2 and CTSH. Results: 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. Conclusions: 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