Department of Immunology, College of Basic Medical Sciences, Central South University, Changsha, China.
Laboratory of Cellular and Molecular Biology, College of Basic Medical Sciences, Central South University, Changsha, China.
Int J Immunogenet. 2024 Feb;51(1):32-38. doi: 10.1111/iji.12647. Epub 2023 Nov 28.
Among the thirteen leukocyte Ig-like receptor (LILR) loci located at 19q13.4, LILRA3 is unique in that it encodes a soluble protein lacking the transmembrane and cytoplasmic domains, and a 6.7 kb deletion spanning the first seven exons has been detected in some human individuals. Presently, there is a lack of data about the distribution of LILRA3 gene deletion in more diverse ethnic groups. Also, no previous studies have investigated the correlation between copy number variation (CNV) of LILRA3 and nasopharyngeal carcinoma (NPC). In this study, five populations from China mainland: two Southern Han populations, Hunan (N = 1478) and Guandong (N = 107); one Southeastern Han population, Fujian (N = 439); and two Northern populations, Inner Mongolia Han (N = 104) and Mongol population from Inner Mongolia (N = 158) were investigated for CNV of LILRA3 using polymerase chain reaction-sequence-specific priming (PCR-SSP) method. LILRA3 variants were also examined in a cohort of NPC cases (N = 1142) in Hunan Han population. The five Chinese populations demonstrated northward increase in frequency of the deleted form of LILRA3 gene (LILRA3Del) (all corrected p values < 0.05). Inter-population comparison also uncovered significant differentiation in the distribution of CNV of LILRA3 among modern human populations. LILRA3Del was found to confer significantly reduced risk to NPC in Hunan Han population (at allelic level: OR = 0.79, 95% CI = 0.71-0.89, p < 0.0001; at genotype level: OR = 0.63, 95% CI = 0.51-0.79, p < 0.0001). No interaction was found between LILRA3 variants and HLA-A02:07, HLA-A11:01, HLA-B13 and HLA-B46:01 alleles in susceptibility to NPC. Our study constitutes the first demonstration of LILRA3 gene as a locus linked to NPC susceptibility in a southern Chinese population. Future independent studies in other populations are warranted to confirm the findings reported in this study.
在位于 19q13.4 的 13 个白细胞免疫球蛋白样受体 (LILR) 基因座中，LILRA3 是独特的，因为它编码一种缺乏跨膜和细胞质结构域的可溶性蛋白，并且在一些人类个体中检测到跨越前七个外显子的 6.7kb 缺失。目前，关于 LILRA3 基因缺失在更多不同种族群体中的分布缺乏数据。此外，以前的研究没有调查 LILRA3 的拷贝数变异 (CNV) 与鼻咽癌 (NPC) 之间的相关性。在这项研究中，我们对来自中国大陆的五个群体进行了 LILRA3 的 CNV 研究：两个南方汉族群体，湖南 (N = 1478) 和广东 (N = 107)；一个东南汉族群体，福建 (N = 439)；以及两个北方群体，内蒙古汉族 (N = 104) 和来自内蒙古的蒙古族 (N = 158)，使用聚合酶链反应-序列特异性引物 (PCR-SSP) 方法。我们还在湖南汉族人群的 NPC 病例队列 (N = 1142) 中检查了 LILRA3 变体。五个中国人群的 LILRA3 基因缺失形式 (LILRA3Del) 的频率呈向北增加的趋势 (所有校正后的 p 值均<0.05)。种群间比较也揭示了现代人类种群中 LILRA3 的 CNV 分布存在显著差异。在湖南汉族人群中，LILRA3Del 显著降低 NPC 的发病风险 (等位基因水平：OR = 0.79，95%CI = 0.71-0.89，p<0.0001；基因型水平：OR = 0.63，95%CI = 0.51-0.79，p<0.0001)。在 NPC 易感性方面，LILRA3 变体与 HLA-A02:07、HLA-A11:01、HLA-B13 和 HLA-B46:01 等位基因之间没有发现相互作用。我们的研究首次证明 LILRA3 基因是一个与中国南方人群 NPC 易感性相关的基因座。需要在其他人群中进行独立的未来研究来证实本研究报告的结果。
