Umamaheswaran Gurusamy
1*, Steven Aibor Dkhar
1, Arun Kumar Annan Sudarsan
1, Katiboina Srinivasa Rao
1, Dharanipragada Kadambari
2, Chandrasekaran Adithan
11 ICMR Centre for Advanced Research in Pharmacogenomics, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry, India
2 Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry, India
Abstract
Introduction:
Decline in circulating estrogen levels cause lessening of bone mass accompanied
with musculoskeletal pain, which is the primary cause for treatment
discontinuation in patients taking aromatase inhibitors. Evidence from the recent
genome-wide association studies (GWAS) suggests
that the genetic variability underlying TCL1A
gene will increase the risk of aromatase inhibitors
(AIs) - induced musculoskeletal toxicity. Currently, no data is
available on the frequency distribution of TCL1A
gene polymorphisms in Indians.
Methods:
In this pilot study, we used TaqMan fluorescent probes to assess the genotypes
of four TCL1A gene polymorphisms associated with
musculoskeletal toxicity in 247 healthy homogenous South Indian subjects on
real time thermocycler. Haplotype estimation and pairwise linkage
disequilibrium (LD) analysis were executed by Haploview.
Results:
The incidence of the polymorphic variant allele (G) frequencies of rs7158782,
rs7159713, rs2369049 and rs11849538 were 21.1%, 23.5%, 18.2% and 22.9%
respectively in the study population. The polymorphisms were found to be in
complete LD with each other. Four different haplotypes, each of which has a
frequency of above 1% were inferred in South Indians using an
expectation-maximization algorithm. Notably, three haplotypes were found to be
population specific viz., H4 A-A-A-G (1.2%) for South India, H5 G-G-A-C (1.3%)
for JPT and H6 G-G-G-C (40.4%) for YRI. Further, H3 G-G-A-G (2.3-16.3%)
haplotype occurs primarily in Asians and virtually absent in Africans. Overall,
the genetic variability and haplotype profile of South Indian population
revealed significant inter-racial variability compared with HapMap data.
Conclusion:
This documentation will contribute for further investigations on the
pharmacogenetics of AIs in South Indians.