TY - JOUR
T1 - HLA class I, KIR, and genome-wide SNP diversity in the RV144 Thai phase 3 HIV vaccine clinical trial
AU - Prentice, Heather A.
AU - Ehrenberg, Philip K.
AU - Baldwin, Karen M.
AU - Geretz, Aviva
AU - Andrews, Charla
AU - Nitayaphan, Sorachai
AU - Rerks-Ngarm, Supachai
AU - Kaewkungwal, Jaranit
AU - Pitisuttithum, Punnee
AU - O'Connell, Robert J.
AU - Robb, Merlin L.
AU - Kim, Jerome H.
AU - Michael, Nelson L.
AU - Thomas, Rasmi
N1 - Funding Information:
Acknowledgments This work was supported by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the US Department of Defense (DOD). This research was funded, in part, by the US National Institute of Allergy and Infectious Disease. The views expressed are those of the authors and should not be construed to represent the positions of the US Army or the DOD. The authors would like to acknowledge Dr. Peter Gilbert (SCHARP, Seattle) and Dr. Mark Milazzo (MHRP, Bethesda) for selecting the placebo-uninfected individuals from the RV144 study. The authors acknowledge Dr. Susan Mason from AFRIMS, Thailand for providing us with the place of origin for the RV144 samples. The authors thank Dr. Arman Bashirova from the National Cancer Institute in Frederick (NCI-Frederick) for sharing the KIR SYBR green assay and Dr. Diane Bolton from MHRP, Silver Spring for use of the Fluidigm BioMark system. The authors also thank Dr. Richard Apps (NCI-Frederick) for helpful comments.
PY - 2014/5
Y1 - 2014/5
N2 - RV144 is the first phase 3 HIV vaccine clinical trial to demonstrate efficacy. This study consisted of more than 8,000 individuals in each arm of the trial, representing the four major regions of Thailand. Human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptor (KIR) genes, as well as 96 genome-wide ancestry informative markers (AIMs) were genotyped in 450 placebo HIV-1-uninfected individuals to identify the immunogenetic diversity and population structure of this cohort. High-resolution genotyping identified the common HLA alleles as A*02:03, A*02:07, A*11:01, A*24:02, A*24:07, A*33:03, B*13:01, B*15:02, B*18:01, B*40:01, B*44:03, B*46:01, B*58:01, C*01:02, C*03:02, C*03:04, C*07:01, C*07:02, C*07:04, and C*08:01. The most frequent three-loci haplotype was B*46:01-C*01:02-A*02:07. Framework genes KIR2DL4, 3DL2, and 3DL3 were present in all samples, and KIR2DL1, 2DL3, 3DL1, 2DS4, and 2DP1 occurred at frequencies greater than 90 %. The combined HLA and KIR profile suggests admixture with neighboring Asian populations. Principal component and correspondence analyses comparing the RV144 samples to the phase 3 International HapMap Project (HapMap3) populations using AIMs corroborated these findings. Structure analyses identified a distinct profile in the Thai population that did not match the Asian or other HapMap3 samples. This shows genetic variability unique to Thais in RV144, making it essential to take into account population stratification while performing genetic association studies. The overall analyses from all three genetic markers indicate that the RV144 samples are representative of the Thai population. This will inform subsequent host genetic analyses in the RV144 cohort and provide insight for future genetic association studies in the Thai population.
AB - RV144 is the first phase 3 HIV vaccine clinical trial to demonstrate efficacy. This study consisted of more than 8,000 individuals in each arm of the trial, representing the four major regions of Thailand. Human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptor (KIR) genes, as well as 96 genome-wide ancestry informative markers (AIMs) were genotyped in 450 placebo HIV-1-uninfected individuals to identify the immunogenetic diversity and population structure of this cohort. High-resolution genotyping identified the common HLA alleles as A*02:03, A*02:07, A*11:01, A*24:02, A*24:07, A*33:03, B*13:01, B*15:02, B*18:01, B*40:01, B*44:03, B*46:01, B*58:01, C*01:02, C*03:02, C*03:04, C*07:01, C*07:02, C*07:04, and C*08:01. The most frequent three-loci haplotype was B*46:01-C*01:02-A*02:07. Framework genes KIR2DL4, 3DL2, and 3DL3 were present in all samples, and KIR2DL1, 2DL3, 3DL1, 2DS4, and 2DP1 occurred at frequencies greater than 90 %. The combined HLA and KIR profile suggests admixture with neighboring Asian populations. Principal component and correspondence analyses comparing the RV144 samples to the phase 3 International HapMap Project (HapMap3) populations using AIMs corroborated these findings. Structure analyses identified a distinct profile in the Thai population that did not match the Asian or other HapMap3 samples. This shows genetic variability unique to Thais in RV144, making it essential to take into account population stratification while performing genetic association studies. The overall analyses from all three genetic markers indicate that the RV144 samples are representative of the Thai population. This will inform subsequent host genetic analyses in the RV144 cohort and provide insight for future genetic association studies in the Thai population.
KW - Ancestry informative markers (AIMs)
KW - Human leukocyte antigen (HLA)
KW - Killer cell immunoglobulin-like receptors (KIR)
KW - Population stratification
KW - RV144
KW - Thailand
UR - http://www.scopus.com/inward/record.url?scp=84899939609&partnerID=8YFLogxK
U2 - 10.1007/s00251-014-0765-6
DO - 10.1007/s00251-014-0765-6
M3 - Article
C2 - 24682434
AN - SCOPUS:84899939609
SN - 0093-7711
VL - 66
SP - 299
EP - 310
JO - Immunogenetics
JF - Immunogenetics
IS - 5
ER -