Characterization Of HLA-F Polymorphism In Four Distinct Populations In Mainland China And3’untranslated Region (3’UTR) Of The MICB Gene In A Northern Chinese Han Population

In the first part of our study, HLA-F allelic typing was performed for690individuals from two southern Chinese Han populations (Hunan Han and Guangdong Han) and two northern Chinese populations (Inner Mongolia Han and Inner Mongolia Mongol). Our data showed that (1)HLA-F*01:01predominated in each population with a frequency>0.94and HLA-F*01:03was relatively more common in the two northern Chinese populations;(2)both geographical and ethnical factors are related to HLA-F allelic distribution, as evidenced by the significant difference in HLA-F allelic distribution between the Hunan Han population and the two northern Chinese populations;(3)significant linkage disequilibrium (LD) was observed for haplotype HLA-A*03-F*01:03in three populations. In most cases, this haplotype extended to HLA-E*01:03; and (4)Ewens-Watterson homozygosity statistic at the HLA-F locus did not depart significantly from expectation in each of the four populations.In the second part of our study,104healthy Han subjects recruited from northern China were investigated for MICB3’UTR allelic variation. Seven polymorphic sites were detected including a2-bp deletion/insertion, a6-bp deletion/insertion and5SNPs. Seven different3’UTR alleles were identified with frequencies ranging from0.0048to0.7981. MICB*005:02exhibited significant linkage disequilibrium (LD) with UTR1; MICB*004:01showed strong LD with both UTR2and UTR3alleles. miRNA hsa-miR-4768-5p, whose seed region binds to positions82-88of MICB3’UTR, encompasses the+11800A/G polymorphism. Ewens-Watterson homozygosity statistics at MICB coding and3’UTR regions were consistent with neutral expectations. Phylogenetic analysis demonstrated the existence of two main MICB lineages.Our result provided for the first time the data of HLA-F allelic distribution in four main ethnic groups in mainland China and the genetic polymorphism of MICB3’UTR in a northern Chinese Han population. The findings are valuable for future studies of population genetics of the non-classical HLA genes residing in the human MHC complex and the mechanisms underlying MICB post-transcriptional regulation. Our data will also inform future studies of the potential role of regulatory region of MICB gene in disease susceptibility in related ethnic groups.