Document Detail


KIR genotypic diversity can track ancestries in heterogeneous populations: a potential confounder for disease association studies.
MedLine Citation:
PMID:  21898189     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Killer cell immunoglobulin-like receptors (KIR) are encoded by highly polymorphic genes that regulate the activation of natural killer (NK) cells and other lymphocyte subsets and likely play key roles in innate and adaptive immunity. Association studies increasingly implicate KIR in disease predisposition and outcome but could be confounded by unknown KIR genetic structure in heterogeneous populations. To examine this, we characterized the diversity of 16 KIR genes in 712 Northern Californians (NC) stratified by self-assigned ethnicities and compared the profiles of KIR polymorphism with other US and global populations using a reference database. Sixty-eight distinct KIR genotypes were characterized: 58 in 457 Caucasians (NCC), 17 in 47 African Americans (NCAA), 21 in 80 Asians (NCA), 20 in 74 Hispanics (NCH), and 18 in 54 "other" ethnicities (NCO). KIR genotype patterns and frequencies in the 4 defined ethnicities were compared with each other and with 34 global populations by phylogenetic analysis. Although there were no population-specific genotypes, the KIR genotype frequency patterns faithfully traced the ancestry of NCC, NCAA, and NCA but not of NCH whose ancestries are known to be more heterogeneous. KIR genotype frequencies can therefore track ethnic ancestries in modern urban populations. Our data emphasize the importance of selecting ethnically matched controls in KIR-based studies to avert spurious associations.
Authors:
Komal Manpreet Singh; Yume T Phung; Mohamed S Kohla; Billy Y-A Lan; Sharon Chan; Diana L Suen; Sahar Murad; Shana Rheault; Peter Davidson; Jennifer Evans; Manpreet Singh; Sofie Dohil; Robert W Osorio; Adil E Wakil; Kimberly Page; Sandy Feng; Stewart L Cooper
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-7
Journal Detail:
Title:  Immunogenetics     Volume:  -     ISSN:  1432-1211     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0420404     Medline TA:  Immunogenetics     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Kalmanovitz Liver Immunology Laboratory, California Pacific Medical Center & Research Institute, 2340 Clay Street, 3rd floor, San Francisco, CA, 94115, USA, singhkm@cpmcri.org.
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