title: Frequency distribution of DNA repair genes ERCC1 and ERCC2 polymorphisms in South Indian healthy population.
abstract: DNA repair genes are crucial in maintaining the integrity of the whole genome. Single nucleotide polymorphisms (SNPs) in DNA repair genes have been attributed to the development of various cancers. SNPs of DNA repair genes (ERCC1 and ERCC2) have been implicated in the causation of various cancers as well as inter-individual variability in the therapeutic outcomes of platinum based therapy. Thus establishing the frequency of these functional SNPs in the healthy population is of significance. The present study was aimed to establish the allele and genotype frequencies of ERCC1 (19007C>T, rs11615; 8092C>A, rs3212986) and ERCC2 (Asp312Asn, rs1799793) genes in South Indian healthy population and to compare the data from HapMap populations. The study population consisted of 128 healthy South Indian unrelated individuals of either sex aged between 18 and 60 years. Standard phenol-chloroform method was used to extract DNA from peripheral leukocytes. The genotype of DNA repair gene polymorphisms was determined by quantitative real-time polymerase chain reaction using TaqMan genotyping assay. The observed frequency of the studied polymorphisms followed Hardy-Weinberg equilibrium (p>0.05). The frequencies of the minor alleles of the SNPs rs11615 (T), rs3212986 (A) and rs1799793 (A) were 43.8%, 29.3% and 35.6%, respectively. Gender-based analysis showed no significant difference in the frequency pattern. The observed allele and genotype frequencies showed significant ethnic difference between South Indians and other HapMap populations. This is the first study to provide the normative frequency data of allele and genotype distribution of three SNPs of ERCC1 and ERCC2 in South Indian healthy population. It might be useful in future genotype-phenotype association studies, especially for predicting the efficacy and adverse events of platinum based drugs.
authors.affiliation: Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry 605006, India. Electronic address: seenuraok@gmail.com.
authors.forename: Katiboina Srinivasa
authors.initials: KS
authors.lastname: Rao
authors.affiliation: Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry 605006, India.
authors.forename: Srinivasamurthy
authors.initials: S
authors.lastname: SureshKumar
authors.affiliation: Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry 605006, India.
authors.forename: Gurusamy
authors.initials: G
authors.lastname: Umamaheswaran
authors.affiliation: Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry 605006, India.
authors.forename: Abialbon
authors.initials: A
authors.lastname: Paul
authors.affiliation: Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry 605006, India.
authors.forename: Biswajit
authors.initials: B
authors.lastname: Dubashi
authors.affiliation: Department of Radiotherapy, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry 605006, India.
authors.forename: Karunanithi
authors.initials: K
authors.lastname: Gunaseelan
authors.affiliation: Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry 605006, India.
authors.forename: Steven Aibor
authors.initials: SA
authors.lastname: Dkhar
mesh_terms: D000293:Adolescent; D000328:Adult; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D064368:Healthy Volunteers; D006801:Humans; D007194:India; D007962:Leukocytes / Q000378:metabolism; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000208:ethnology* / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
keywords: DNA repair genes; ERCC; Platinum drugs; South Indian