Association of HLA class I and class II alleles with bullous pemphigoid in Chinese Hans
JOURNAL OF DERMATOLOGICAL SCIENCE
Authors: Fang, Hui; Shen, Shengxian; Zheng, Xiaodong; Dang, Erle; Zhang, Jieyu; Shao, Shuai; Qiao, Pei; Li, Qiuju; Wang, Hua; Li, Caixia; Sun, Liangdan; Wang, Gang
Abstract
Background: Bullous pemphigoid (BP) is one of the most common autoimmune skin diseases. Associations of genes, especially human leukocyte antigen (HLA)-DQalleles, with BP indicate that genetic predisposition contributes to the disease. Objectives: To evaluate the association of HLA class I and HLA class II alleles with susceptibility to BP in the northern Chinese Han population. Methods: We performed genotype for HLA-A, -B, -C, -G, -DPAI, -DPBI, -DQAI, -DQB1 and -DRBI loci in 105 patients with BP by Sanger sequence-based typing (SBT) method. These data were compared with a local control cohort of 420 age- and sex-matched cases. Results: Among the HLA alleles described herein, the susceptibility alleles associated with a high prevalence of BP were A*11:01 (OR = 1.9 Pc = 0.017); B*37:01 (OR= 8, Pc = 1.811 x 10(-6)); G*01:01 (OR= 3.61, Pc = 2.839 x 10(-15)) and G*01:06 (OR= 2.22, Pc = 0.025); DQAI*01:05 (OR= 4.87, Pc = 5.822 x 10(-5)), DQAI*05:05 (OR= 2.64, Pc= 9.114 x 10(-4)), and DQAI*05:08 (OR= 10.2, Pc= 0.016); DQB1*03:01 (OR =1.69, Pc = 0.048) and DQB1*05:01 (OR = 3.42, Pc = 7.28 x 10(-6)); and DRBI*10:01 (OR= 6.85, Pc= 2.63 x 10(-6)). To the contrary, HLA-DQA1*01:02 (OR= 0.46, Pc= 8.603 x 10(-4)) and DQAI*01:03 (OR= 0.38, Pc= 0.048); DQBI*02:02 (OR= 0.28, Pc= 0.016); and DRBI*07:01 (OR= 0.26, Pc = 0.004) had significant associations with protection against BP. In addition, the frequency of haplotype HLA-DRB1*13-DQA1*05-DQB1*03 (OR= 12.32, Pc = 0.026) in BP patients was significantly higher than those in controls. Conclusion: Our data demonstrated that the alleles and haplotypes found in this study may be important differential genetic markers for susceptibility to or protection against BP in individuals of northern Chinese Han population. 2017 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
A time transect of exomes from a Native American population before and after European contact
NATURE COMMUNICATIONS
Authors: Lindo, John; Huerta-Sanchez, Emilia; Nakagome, Shigeki; Rasmussen, Morten; Petzelt, Barbara; Mitchell, Joycelynn; Cybulski, Jerome S.; Willerslev, Eske; DeGiorgio, Michael; Malhi, Ripan S.
Abstract
A major factor for the population decline of Native Americans after European contact has been attributed to infectious disease susceptibility. To investigate whether a pre-existing genetic component contributed to this phenomenon, here we analyse 50 exomes of a continuous population from the Northwest Coast of North America, dating from before and after European contact. We model the population collapse after European contact, inferring a 57% reduction in effective population size. We also identify signatures of positive selection on immune-related genes in the ancient but not the modern group, with the strongest signal deriving from the human leucocyte antigen (HLA) gene HLA-DQA1. The modern individuals show a marked frequency decrease in the same alleles, likely due to the environmental change associated with European colonization, whereby negative selection may have acted on the same gene after contact. The evident shift in selection pressures correlates to the regional European-borne epidemics of the 1800s.