Roberto Taramelli

Evidence that apolipoprotein(a) phenoptype is a risk factor for coronary artery disease in men < 55 years of age

Whereas the importance of plasma lipoprotein(a) [Lp(a)] levels as a risk factor for premature coronary artery disease (CAD) is certain, it is not clear if the apolipoprotein(a) [apo(a)] phenotype plays an additional and independent role. To investigate the possible effect of apo(a) phenotype on premature CAD (in patients < 55 years of age), plasma Lp(a) concentrations, the apo(a) phenotypes, and their relation with many recognized CAD risk factors were examined in 96 non-diabetic male patients with angiographically defined CAD and in 83 age-matched male control subjects with no angiographic evidence of CAD. Results demonstrate that patients with premature CAD are characterized by higher Lp(a) levels (24 +/- 21 vs 17 +/- 15 mg/dl, p < 0.01) and a higher frequency of S2 phenotype (32% vs 15%, p < 0.01). Patients with an S2 phenotype exhibited significantly higher plasma Lp(a) concentrations than control subjects with the same isoform (37 +/- 22 vs 22 +/- 17 mg/dl, p < 0.05). A significant correlation was found between apo B and Lp(a) levels in patients with an S2 phenotype. In addition, patients had a low frequency of S1 and S4, and a high frequency of double-band phenotypes of apo(a). Multivariate analysis did not demonstrate an independent role for apo(a) phenotype as a risk factor for premature CAD. In conclusion, CAD patients < 55 years of age have a very different pattern of apo(a) phenotypes than subjects with no angiographic evidence of CAD; this study confirms the hypothesis that apo(a) phenotype may play an additional role in the etiology of premature CAD.

Short direct repeats at the breakpoints of a novel large deletion in the CFTR gene suggest a likely slipped mispairing mechanism

Abstract In the cystic fibrosis conductance transmembrane regulator (CFTR) gene a few small deletions and only a large, complex, 50-kb deletion have been described so far. We report a second large deletion, which had been hypothesized in a patient affected by cystic fibrosis on the basis of an abnormal pattern of inheritance of the intragenic microsatellites IVS17b/TA and IVS17b/CA. Southern blot analysis revealed the presence of an anomalous band in the patient and her father, in the region encompassing exons 13 – 19, approximately 0.6 kb shorten than the one present in normal controls, in addition to the band of the correct size. Cloning and sequencing the DNA fragments spanning the region of interest demonstrated the presence of a 703-bp deletion causing complete removal of exon 17b in the paternal cystic fibrosis chromosome. This analysis revealed the presence of two short direct repeats flanking the breakpoints. The 3′ repeat partially overlapped the IVS17b/CA microsatellite and the number of CA repeated units present in the paternal cystic fibrosis allele was the shortest ever found among chromosomes so far analyzed. These data may suggest that the mechanism for the generation of the deletion may have involved a slipped mispairing during DNA replication, which has not previously been described in the CFTR gene.

A recombination event in the closely linked plasminogen and apolipoprotein(a) gene loci.

Genetic studies as well as in situ hybridisation data have strongly demonstrated that the genes coding for apoprotein(a) and plasminogen are linked and localised to chromosome 6 at band 6q26‐27. We describe in this report the presence of a recombination event in a region of approximately 50 kb of DNA separating the two genes. The recombination was found in an Italian family, in which a mutation affecting both plasminogen plasma level and activity of plasminogen activity has been detected. Polymerase chain reaction and sequencing analysis showed the presence of a mutation different from those previouly reported in two Japanese families.