Analysis of Polymorphisms in the 5’-Flanking Region of the Apolipoprotein(a) [Apo(a)] Gene in Thai Subjects with Coronary Artery Diseases
Nednapis Tirawanchai PhD*, Wattana Leowattana MD, PhD**, Anchaleekorn Somkasetrin MSc*, Pushdee Thongsaen MSc*
Affiliation : * Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok ** Faculty of Tropical Medicine, Mahidol University, Bangkok
Lipoprotein(a) [Lp(a)] is a complex lipoprotein particle in human plasma. It is composed of apolipoprotein B (Apo B)-100 and apolipoprotein(a) which are linked by a disulfide bond. Plasma levels of the Lp(a) vary greatly (over 1,000 folds) among individuals. Elevated plasma levels of the Lp(a) have been shown to be an independent risk factor for coronary artery diseases (CAD). The level of Lp(a) is controlled by a single gene, the Apo(a) gene, with multiple alleles; each encodes different concentrations of the Lp(a). Previous studies revealed the presence of polymorphisms in the 5’-flanking region (FL) of the Apo(a) gene at 3 positions: G or A (-914), C or T (-49), and G or A (-21), which can be detected by cleavage of PCR-amplified DNA products with TaqI, MaeII and HhaI, respectively. The 5’-FL genotypes of the Apo(a) gene can be classified by the combination of the presence (+) or absence (-) of these restriction sites into 5 types; type A, +++, type B, -++, type C, -+-, type D, --+ and type E, +-+. In the present study, the authors analyzed the 5’FL types of the Apo(a) gene by polymerase chain reaction and restriction fragment length polymorphism (PCR- RFLP) in 100 healthy control subjects, 26 CAD patients with [Lp(a)] < 30 mg/dL, and 94 CAD patients with [Lp(a)] > 30 mg/dL. The authors found that the genotype frequencies of the Apo(a) gene were 53, 16, 27 and 4%, for types A, B, C and D respectively in normal healthy controls. In CAD patients with [Lp(a)] < 30 mg/dL, the distribution of the genotype frequencies were 53.8, 11.5, 30.8 and 3.9% for types A, B, C and D, respectively. Additionally in CAD patients with [Lp(a)] > 30 mg/dL, the genotype frequencies were 60.6, 11.7, 21.3 and 6.4% for types A, B, C and D, respectively. The present study might shed some light to understand CAD at the molecular level.
Keywords : Coronary artery diseases, Lipoprotein(a) [Lp(a)], Polymorphism
