title: Genetic variations of NR1I3 and NR2B1 in Asian populations.
abstract: Several nuclear receptors are being increasingly recognized for their role as master xenosensors. Among them, CAR-RXRα heterodimer, as encoded by NR1I3 and NR2B1, responds to the presence of drug compounds and regulates the transcription of a wide array of genes involved in their disposition. To investigate the frequency distribution and linkage disequilibrium patterns of NR1I3 and NR2B1 genetic variations, these genes were screened in 168 healthy local Asian subjects, namely Chinese, Malays, and Indians (n=56 subjects each). A total of 38 and 88 SNPs were identified in NR1I3 and NR2B1, respectively. Among them, there were 13 and 43 novel SNPs present at low allelic frequencies (<10%) in NR1I3 and NR2B1, respectively. Notably, the genetic variations in the NR1I3 and NR2B1 genes were mainly confined to the introns whilst the exons were highly conserved across the ethnic populations. Indians harboured distinct frequency distributions from Chinese and Malays in both genes. Based on the linkage disequilibrium patterns of both genes, a number of tag-SNPs were selected for each population (n=8-13 for NR1I3; n=12-18 for NR2B1). In-silico prediction analyses revealed a number of possible functional SNPs. Our data would be valuable for future pharmacogenetic studies on the drug substrates of CAR-RXRα target genes.
authors: Laboratory of Clinical Pharmacology, Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore, Singapore.
authors: Sin Chi
authors: SC
authors: Chew
authors: Joanne Siok Liu
authors: JS
authors: Lim
authors: Onkar
authors: O
authors: Singh
authors: Mabel
authors: M
authors: Wong
authors: Edmund J D
authors: EJ
authors: Lee
authors: Balram
authors: B
authors: Chowbay
mesh_terms: D044466:Asian People / Q000235:genetics*; D000090702:Constitutive Androstane Receptor; D005091:Exons / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D047490:Retinoid X Receptor alpha / Q000235:genetics*
chemical_list: D000090702:Constitutive Androstane Receptor; C000716327:NR1I3 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D047490:Retinoid X Receptor alpha