Regarding "haptoglobin 2-1 phenotype predicts rapid growth of abdominal aortic aneurysms"

I have read with great interest the recent work of Wiernicki et al, which reports a strong association of Hp 2*/1* phenotype with increased rates of expansion of abdominal aortic aneurysm (AAA) and higher serum elastase activity and C-reactive protein levels. The authors report a detailed analysis of clinical biochemistry markers and characteristics of patients enrolled in the study. However, the interpretation of this study needs to take into account the molecular and genetic complexity of haptoglobin (Hp) polymorphism. The authors failed to explain why the Hp 2*/1* heterozygous phenotype was different from both homozygous phenotypes, and speculated that Hp 2*/1* phenotype might cumulate harmful features associated with allele Hp*1 (stimulation of the elastin hydrolysis) and allele Hp*2 (increased risk of atherosclerosis) to yield a combination that is particularly efficient in promoting AAA growth.The reason underlying the association of Hp 2*/1* phenotype with increased rates of expansion of AAA resides in the phenomenon of molecular heterosis at Hp 1/2 polymorphism, reported by several genetic association studies, and further confirmed by molecular structure of haptoglobin protein. Molecular heterosis occurs when subjects heterozygous for a specific genetic polymorphism show a significantly greater effect (positive heterosis) or lesser effect (negative heterosis) for a quantitative or dichotomous trait than subjects homozygous for either allele. Comings and MacMurray estimated that molecular heterosis may occur in up to 50% of gene associations.