Multiple low-frequency and rareHLA-Ballelic variants are associated with reduced risk in 1,105 nasopharyngeal carcinoma patients in Hunan province, southern China
INTERNATIONAL JOURNAL OF CANCER
Authors: Tian, Wei; Zhu, FaMing; Cai, JinHong; Li, LiXin; Jin, HeKun; Wang, WenYi
Abstract
In our study, 1,105 cases of nasopharyngeal carcinoma (NPC) and 1,430 normal controls recruited from Hunan province, southern China were typed for human leukocyte antigen (HLA)-Blocus by Sanger sequencing exons 2-4. Besides confirming the NPC association withHLA-B*46:01allele,HLA-A*02:07-B*46:01andHLA-A*33:03-B*58:01haplotypes (all positive), andHLA-B*13lineage (negative), all of which were relatively common, strong negative associations were observed for five low-frequency and rare alleles or lineages, includingHLA-B*07,-B*27:04,-B*39,-B*51:02and-B*55:02, with odds ratio (OR) ranging from 0.16 to 0.3 (allp(corrected)< 0.05). These strong protective associations were independent of linkage disequilibrium (LD) betweenHLA-AandHLA-Bloci. Further analysis indicated a single amino acid change from histidine to tyrosine at residue 171 is probably crucial for the mutant allele,HLA-B*51:02, to mediate resistance to NPC. A subset of NPC cases (n= 821) and normal controls (n= 1,035) were tested for antivirus capsid antigen immunoglobulin A (anti-VCA IgA), which differed drastically between the two groups [67.7%vs. 5.5%, OR (95% confidence interval) = 36 (26.55-48.81),p <0.0001].HLA-Ballelic variation did not associate with seropositivity for anti-VCA IgA in either group. Results from our study show, more clearly than previously, the existence of a cluster of low-frequency and rareHLA-Bvariants conferring low, or very low risk to NPC, a phenomenon not observed in other ethnic groups. Our data shed new insights into genetic susceptibility to NPC in southern Chinese populations. Future independent studies are warranted to replicate the findings reported in our study.
High resolution allele genotyping and haplotype frequencies for NGS based HLA 11 loci of 5266 Hong Kong Chinese bone marrow donors
HUMAN IMMUNOLOGY
Authors: Kwok, Janette; Tang, W. H.; Chu, W. K.; Chan, Y. S.; Liu, Zhongyi; Yang, Wanling; Ip, Patrick; Ma, Wen; Lee, C. K.; Middleton, Derek
Abstract
Next-generation sequencing (NGS) at the HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 loci was performed on 5,266 southern Chinese unrelated donors of the Hong Kong Bone Marrow Donor Registry. High-resolution HLA genotypes defined by full sequencing of class I loci and extended coverage of class II loci were attained to determine allele frequencies and estimate haplotype frequencies. This study provides allele and haplotype frequencies on 11 loci estimated for the first time in the Hong Kong Chinese population. These results describe extended haplotypes including the less frequently typed HLA-DPA1, -DPB1 and -DQA1 loci and distinctive haplotype associations. The present data are timely in that they allow the permissible matching in HLA-DPB1 for Chinese patients awaiting haematopoietic stem cell transplantation upon applying the latest requirement of NMDP matching guidelines. Overall, these results provide a useful reference source for population genetics studies, HLA-disease association studies and for improving donor recruitment and selection strategies of bone marrow registries. The allele and haplotype data are available in the Allele Frequencies Net Database under the population name "Hong Kong Chinese HKBMDR, HLA 11 loci'' and the identifier (AFND3724) [1].