SNP variants associated with non-Hodgkin lymphoma (NHL) correlate with human leukocyte antigen (HLA) class II expression

• Published in: Scientific reports Vol. 7; no. 1; p. 41400
• Main Authors: Ten, Lik-Chin, Chin, Yoon-Ming, Tai, Mei-Chee, Chin, Edmund Fui-Min, Lim, Yat-Yuen, Suthandiram, Sujatha, Chang, Kian-Meng, Ong, Tee-Chuan, Bee, Ping-Chong, Mohamed, Zahurin, Gan, Gin-Gin, Ng, Ching-Ching
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 31.01.2017
• Subjects: Antigens; Etiology; Genome-wide association studies; Genomes; Histocompatibility antigen HLA; Lymphocytes B; Lymphoma; Minority & ethnic groups; Single-nucleotide polymorphism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep41400

Large consortia efforts and genome-wide association studies (GWASs) have linked a number of genetic variants within the 6p21 chromosomal region to non-Hodgkin lymphoma (NHL). Complementing these efforts, we genotyped previously reported SNPs in the human leukocyte antigen (HLA) class I (rs6457327) and class II (rs9271100, rs2647012 and rs10484561) regions in a total of 1,145 subjects (567 NHL cases and 578 healthy controls) from two major ethnic groups in Malaysia, the Malays and the Chinese. We identified a NHL-associated (P  = 0.0008; OR  = 0.54; 95% CI = 0.37-0.77) and B-cell associated (P  = 0.0007; OR  = 0.51; 95% CI = 0.35-0.76) SNP rs2647012 in the Malaysian Malays. In silico cis-eQTL analysis of rs2647012 suggests potential regulatory function of nearby HLA class II molecules. Minor allele rs2647012-T is linked to higher expression of HLA-DQB1, rendering a protective effect to NHL risk. Our findings suggest that the HLA class II region plays an important role in NHL etiology.