Molecular evolution of immunoglobulin superfamily genes in primates
IMMUNOGENETICS
Authors: Ohtani, Hitoshi; Nakajima, Toshiaki; Akari, Hirofumi; Ishida, Takafumi; Kimura, Akinori
Abstract
Genes of the immunoglobulin superfamily (IgSF) have a wide variety of cellular activities. In this study, we investigated molecular evolution of IgSF genes in primates by comparing orthologous sequences of 249 IgSF genes among human, chimpanzee, orangutan, rhesus macaque, and common marmoset. To evaluate the non-synonymous/synonymous substitution ratio (omega), we applied Bn-Bs program and PAML program. IgSF genes were classified into 11 functional categories based on the Gene Ontology (GO) database. Among them, IgSF genes in three functional categories, immune system process (GO: 0002376), defense response (GO: 0006952), and multi-organism process (GO: 0051704), which are tightly linked to the regulation of immune system had much higher values of. than genes in the other GO categories. In addition, we estimated the average values of. for each primate lineage. Although each primate lineage had comparable average values of., the human lineage showed the lowest. value for the immune-related genes. Furthermore, 11 IgSF genes, SIGLEC5, SLAMF6, CD33, CD3E, CEACAM8, CD3G, FCER1A, CD48, CD4, TIM4, and FCGR2A, were implied to have been under positive selective pressure during the course of primate evolution. Further sequence analyses of CD3E and CD3G from 23 primate species suggested that the Ig domains of CD3E and CD3G underwent the positive Darwinian selection.
Genetic variation in FCER1A predicts peginterferon alfa-2a-induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B
JOURNAL OF VIRAL HEPATITIS
Authors: Wei, Lai; Pavlovic, Vedran; Bansal, Aruna T.; Chen, Xiaoping; Foster, Graham R.; He, Hua; Kao, Jia-Horng; Lampertico, Pietro; Liaw, Yun-Fan; Motoc, Adriana; Papatheodoridis, George, V; Piratvisuth, Teerha; Plesniak, Robert; Wat, Cynthia
Abstract
In a multicentre, genome-wide association study to identify host genetic factors associated with treatment response in adult chronic hepatitis B patients, genotype data were obtained by microarray analysis from 1669 patients who received peginterferon alfa-2a for >= 24 weeks with/without a nucleos(t)ide analog. Treatment response was assessed at least 24 weeks post-treatment, using serological and/or virological endpoints. Thirty-six single-marker analyses and a gene-by-gene analysis were conducted. No single nucleotide polymorphisms (SNPs) achieved genome-wide significance (P < 5 x 10(-8)) in single-marker analyses, but suggestive associations (P < 1 x 10(-5)) were identified for 116 SNPs. In gene-by-gene analyses, one gene, FCER1A (rs7549785), reached genome-wide significance (P = 2.65 x 10(-8)) in East Asian patients for hepatitis B surface antigen (HBsAg) clearance, with a moderate effect size (odds ratio = 4.74). Eleven of 44 carriers (25%) of the A allele at rs7549785 achieved HBsAg clearance compared with 69/1051 (7%) noncarriers. FCER1A encodes the alpha subunit of the immunoglobulin E receptor. In a post hoc analysis of a homogenous patient subset, the strongest intragenic association was for rs7712322 (POLR3G, P = 7.21 x 10(-7)). POLR3G encodes the G subunit of the polymerase (RNA) III enzyme, involved in sensing and limiting infection by intracellular bacteria and DNA viruses, and as a DNA sensor in innate immune responses. FCER1A (rs7549785) and possibly POLR3G (rs7712322) are shown to be associated with peginterferon alfa-2a response in adult patients with chronic hepatitis B. Independent confirmation of these findings is warranted (clinicaltrials.gov number NCT01855997).