Prevalence of genetic variants associated with cardiovascular disease risk and drug response in the Southern Indian population of Kerala.
OBJECTIVE
This study reports the prevalence of five clinically significant variants associated with increased risk of cardiovascular disorders, and variable responses of individuals to commonly prescribed cardiovascular drugs in a South Indian population from the state of Kerala.


METHODS
Genomic DNA isolated from 100 out-patient samples from Kerala were sequenced to examine the frequency of clinically relevant polymorphisms in the genes MYBPC3 (cardiomyopathy), SLCO1B1 (statin-induced myopathy), CYP2C9, VKORC1 (response to warfarin) and CYP2C19 (response to clopidogrel).


RESULTS
Our analyses revealed the frequency of a 25 bp deletion variant of MYBPC3 associated with risk of cardiomyopathy was 7%, and the SLCO1B1 "C" allele associated with risk for statin-induced myopathy was 15% in this sample group. Among the other variants associated with dose-induced toxicity of warfarin, VKORC1 (c.1639G>A), was detected at 22%, while CYP2C9*3 and CYP2C9*2 alleles were present at a frequency of 15% and 3% respectively. Significantly, the tested sample population showed high prevalence (66%) of CYP2C19*2 variant, which determines response to clopidogrel therapy.


CONCLUSIONS
We have identified that certain variants associated with cardiovascular disease and related drug response in the five genes, especially those in VKORC1, CYP2C19 and MYBPC3, are highly prevalent in the Kerala population, with almost 2 times higher prevalence of CYP2C19*2 variant compared with other regions in the country. Since the variants chosen in this study have relevance in disease phenotype and/or drug response, and are detected at a higher frequency, this study is likely to encourage clinicians to perform genetic testing before prescribing therapy.
MedGenome (Division of Molecular Diagnostics), SciGenom Labs Pvt. Ltd, CSEZ, Kakkanad, Cochin, Kerala, India.
Lakshmi
L
Mahadevan
MedGenome (Division of Molecular Diagnostics), SciGenom Labs Pvt. Ltd, CSEZ, Kakkanad, Cochin, Kerala, India.
Ancy
A
Yesudas
MedGenome (Division of Molecular Diagnostics), SciGenom Labs Pvt. Ltd, CSEZ, Kakkanad, Cochin, Kerala, India.
P K
PK
Sajesh
MedGenome (Division of Molecular Diagnostics), SciGenom Labs Pvt. Ltd, CSEZ, Kakkanad, Cochin, Kerala, India.
S
S
Revu
MedGenome (Division of Molecular Diagnostics), SciGenom Labs Pvt. Ltd, CSEZ, Kakkanad, Cochin, Kerala, India.
Prasanna
P
Kumar
MedGenome (Division of Molecular Diagnostics), SciGenom Labs Pvt. Ltd, CSEZ, Kakkanad, Cochin, Kerala, India.
Devi
D
Santhosh
MedGenome (Division of Molecular Diagnostics), SciGenom Labs Pvt. Ltd, CSEZ, Kakkanad, Cochin, Kerala, India.
Sam
S
Santhosh
Department of Biotechnology, Karpagam University, Coimbatore, Tamil Nadu, India.
J M
JM
Sashikumar
Department of Biochemistry, Karpagam University, Coimbatore, Tamil Nadu, India.
V K
VK
Gopalakrishnan
Meditrina Cardiac Centre, St. Thomas Hospital, Changanassery, Kerala, India.
Joji
J
Boben
MedGenome (Division of Molecular Diagnostics), SciGenom Labs Pvt. Ltd, CSEZ, Kakkanad, Cochin, Kerala, India.
Changanamkandath
C
Rajesh
Cardiovascular disease; drug response; drug toxicity; genetic testing