Effect of genetic variant (rs11887534) in ABCG8 gene in coronary artery disease and response to atorvastatin therapy.
BACKGROUND
ATP-binding cassette transporter ABCG8 plays an important role in excretion of cholesterol from liver. Common genetic polymorphisms in ABCG8 gene may genetically predispose an individual to coronary artery disease (CAD) along with response to atorvastatin therapy. Thus, we aimed to examine the role of ABCG8 D19H polymorphism (rs11887534) in susceptibility to CAD and its influence on atorvastatin response.


METHODS
The study included 213 CAD patients and 220 controls. Genotyping of ABCG8 D19H polymorphism was done by PCR-RFLP.


RESULTS
Our results showed that ABCG8 'H' allele was conferring significant risk for CAD in a dominant model (OR=2.54; p=0.014). This increased risk for CAD was more pronounced in males (OR=2.69; p=0.030). No correlation of ABCG8 genotypes with the risk factors (diabetes, hypertension and smoking) of CAD was observed. On atorvastatin treatment there was a significant decrease in the LDL-C levels (p=0.021). However, stepwise multiple regression analysis showed that this decease was not associated with ABCG8 genetic variant (p=0.845). Observed determinants of variation in interindividual response to atorvastatin therapy were pre-treatment LDL-C (p= 0.024) and TC (p=0.017).


CONCLUSIONS
Although the genetic variant 19H of ABCG8 confers risk for CAD in North Indian population, it is not associated with interindividual response to atorvastatin therapy.
Srivastava
Anshika
A
Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.
Garg
Naveen
N
Srivastava
Anvesha
A
Srivastava
Kshitij
K
Mittal
Balraj
B
D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D008055:Lipids / Q000032:analysis; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011758:Pyrroles / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome
C416946:ABCG8 protein, human; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D000069059:Atorvastatin