CD36 is a class B scavenger receptor recognizing a variety of ligands including long-chain fatty acids and modified LDL. We investigated whether genetic variability at this locus is a determinant of free fatty acid (FFA) plasma levels and risk of coronary artery disease (CAD) in Caucasians. Typing of 21 polymorphic markers, evenly spanning the CD36 gene, revealed two linkage disequilibrium (LD) blocks that could be tagged by five polymorphisms (-33137A>G, -31118G>A, 25444G>A, 27645del>ins and 30294G>C). In 585 non-diabetic individuals of Caucasian origin, the 30294G>C polymorphism was significantly associated with FFA levels (P = 0.02)--an effect that was especially visible among men (P = 0.009). A similar association was observed in this gender at -33137 (P = 0.008) and -31118 (P = 0.028). When the five tag polymorphisms were considered together, men carrying the AGGIG haplotype had 31% higher FFA (P = 0.0002) and 20% higher triglycerides (P = 0.025) than non-carriers. The same haplotype was associated with increased risk of CAD in 197 type 2 diabetic individuals from the US (OR = 2.3, 95% CI 1.2-4.2). A similar tendency was observed in a group of 321 type 2 diabetic individuals from Italy (OR = 1.4, 0.9-2.3), resulting in an overall relative risk of 1.6 (1.1-2.3, P = 0.015) in the two populations considered together. By targeted resequencing, we identified a common variant in the CD36 promoter that is in strong LD with the AGGIG haplotype and could be partly responsible for these findings. In conclusion, this comprehensive study of CD36 variability indicates that the common polymorphisms at this locus modulate lipid metabolism and cardiovascular risk in Caucasians.
Introduction
Percutaneous coronary intervention (PCI) in patients with congenital coagulation factor deficiencies presents a unique challenge. They are not only at increased risk of perioperative bleeding but can also suffer thrombosis of the stent since preventive anticoagulation and antiplatelet therapy is difficult. Several cases of successful PCI have been described in patients with hemophilias A and B, but there are no reports in patients with combined coagulation factor deficiencies.
Aim
We used PCI to treat the coronary artery disease in a patient with the combined deficiency of factor V and factor VIII (F5F8D) and analyzed the molecular basis of the disorder for this patient.
Methods
A 68 year old patient was admitted for urgent PCI with bare metal stent placement after the diagnosis of the combined deficiency of F5F8D. Peripheral blood DNA was extracted for the sequence analysis of LMAN1 and MCFD2 genes. Mutation in LMAN1 was confirmed by molecular cloning of the PCR product and resequencing of the resulting clones.
Results
The patient underwent successful PCI with good long-term outcome. He tolerated well anticoagulation therapy with unfractionated heparin and double antiplatelet therapy while he was initially supported with fresh frozen plama and recombinant FVIII. Molecular analysis revealed that the patient carries unusual compound heterozygous frameshift mutations on the same microsatellite repeat region in exon 8 of LMAN1, one of which is a novel mutation (c.912delA).
Conclusion
Our results suggest that patients with F5F8D can safely undergo PCI for coronary artery disease, with the treatment individualized to the specific patient.
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