陶玉芬,史磊,姚宇峰,史荔,刘舒媛
TAO Yufen,SHI Lei,YAO Yufeng,SHI Li,LIU Shuyuan

• 1:中国医学科学院&北京协和医学院医学生物学研究所

摘要(Abstract)：

目的:探讨趋化因子受体5(CCR5)Δ32突变在中国20个民族群体中的扩散特征。方法:选取中国20个不同民族共计2 788例健康无关个体,抽取外周静脉血提取基因组DNA,采用PCR检测CCR5Δ32突变(结果进行测序验证),分析CCR5Δ32突变在中国20个民族群体中的分布情况,了解CCR5Δ32突变在中国人群中的扩散特征。结果:鄂温克族、回族(宁夏)、塔吉克族中各检测到1例CCR5Δ32基因突变杂合子(rs333 wt/mt),CCR5Δ32突变的频率分别为1. 25%、0. 68%及1. 11%;在云南汉族群体中检测到2例CCR5Δ32基因突变杂合子(rs333 wt/mt),CCR5Δ32突变的频率为0. 04%;其余群体中均未检测到CCR5Δ32基因突变。结论:CCR5Δ32基因突变在北方群体分布较多,符合"北高南低"的趋势。
Objective: To investigate the diffusion characteristics of CCR5 Δ32 mutation in 20 ethnic groups in China. Methods: 2 788 healthy individuals of 20 different ethnic groups in China were selected,and genomic DNA from peripheral venous blood was extracted. The distribution of CCR5 Δ32 mutation in 20 ethnic groups in China was analyzed by PCR detection( the results were verified by sequencing),and the diffusion characteristics of CCR5 Δ32 mutation in Chinese population were understood. Results: A case of heterozygous mutation of CCR5 Δ32 gene( rs333 wt/mt) was detected in Ewenki,Hui( Ningxia) and Tajik. CCR5 Δ32 mutation frequencies were 1. 25%,0. 68% and1. 11%,respectively. The mutation heterozygote( rs333 wt/mt) of CCR5 Δ32 gene was detected in 2 cases in Han population of Yunnan,and the frequency of mutation was 0. 04%. CCR5 Δ32 mutations were not detected in the rest of the population. Conclusion: CCR5 Δ32 gene mutation is more distributed in the northern population,which accords with the trend of " north is high and south is low".

关键词(KeyWords)： 基因频率;趋化因子受体5;民族;群体;基因突变;Δ32突变
gene frequency;chemokine receptor 5(CCR5);nationality;population;gene mutation;Δ32 mutation

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金青年科学基金项目(31401063)

作者(Author): 陶玉芬,史磊,姚宇峰,史荔,刘舒媛
TAO Yufen,SHI Lei,YAO Yufeng,SHI Li,LIU Shuyuan

DOI: 10.19367/j.cnki.2096-8388.2020.05.004

参考文献(References)：

• [1] BLANPAIN C,LEE B,TACKOEN M,et al. Multiple nonfunctional alleles of CCR5 are frequent in various human populations[J]. Blood, 2000,96(5):1638-1645.
• [2]VENUTI A,PASTORI C,LOPALCO L. The Role of Natural antibodies to CC chemokine receptor 5 in HIV infection[J]. Front Immunol,2017,8:1358.
• [3]HEREDIA J,PARK J,BRUBAKER R,et al. Mapping interaction sites on human chemokine receptors by deep mutational scanning[J]. J Immunol,2018,200(11):3825-3839.
• [4]LIU R,PAXTON W,CHOE S,et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection[J]. Cell,1996,86(3):367-377.
• [5]SAMSON M,LIBERT F,DORANZ B,et al. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene[J].Nature,1996,382(6593):722-725.
• [6]GUPTA R,ABDUL-JAWAD S,MCCOY L,et al. HIV-1remission following CCR5Δ32/Δ32 haematopoietic stemcell transplantation[J]. Nature,2019,568(7751):244-248.
• [7]HUTTER G,GANEPOLA S. The CCR5-delta32 polymorphism as a model to study host adaptation against infectious diseases and to develop new treatment strategies[J]. Expe Bio Med(Maywood),2011,236(8):938-943.
• [8]BLANPAIN C,MIGEOTTE I,LEE B,et al. CCR5 binds multiple CC-chemokines:MCP-3 Acts as a natural antagonist[J]. Blood,1999,94(6):1899-1905.
• [9]贺小峰，贾宇静，苏娇，等．中国人群CCR5△32、CCR2-64I、SDF1-3’A基因多态性与HIV-1感染相关性的Meta分析[J]．南方医科大学学报，2011,31(5):791-795.
• [10]唐慧，郭淑霞，赵蓉莉，等．新疆维吾尔族HIV高危人群OOR5△32多态性与艾滋病的关系[J]．石河子大学学报(自然科学版)，2010(2):198-201.
• [11]WANG F S,HONG W G,CAO Y,et al. Population survey of CCR5 delta32,CCR5 m303,CCR2b 64I,and SDF1 3'A allele frequencies in indigenous Chinese healthy individuals,and in HIV-1-infected and HIV-1-uninfected individuals in HIV-1 risk groups[J]. J Acquir Immune Defic Syndr,2003,32(2):124-130.
• [12]叶俊生，王福生，彭林，等．中国傣族、景颇族人群中与艾滋病相关的CCR5△32、CCR2b-64I、SDF1-3'A等位基因多态性分布[J]．遗传，2003,25(6):655-659.
• [13]麦志丹，臧宁，苏齐鉴，等．广西壮、汉族人群HIV-1感染相关基因CCR2—64I和SDF1-3’A多态性的研究[J]．现代预防医学，2009,36(20):3804-3805.
• [14]邓小玲，洪坤学，陈健平，等．四川彝族人群HIV-1辅助受体CCR5△32和CCR2-64I基因多态性分析[J]．中华流行病学杂志，2004,25(12):1050-1053.
• [15]MULLER-TRUTWIN M,CORBET S,HANSEN J,et al.Mutations in CCR5-coding sequences are not associated with SIV carrier status in African nonhuman primates[J]. AIDS Res Hum Retroviruses,1999,15(10):931-939.
• [16]MARTINSON J,CHAPMAN N,REES D,et al. Global distribution of the CCR5 gene 32-basepair deletion[J].Nat Genet,1997,16(1):100-103.
• [17]YUDIN N,VINOGRADOV S,POTAPOVA T,et al.Distribution of CCR5-delta 32 gene deletion across the Russian part of Eurasia[J]. Human genetics,1998,102(6):695-698.
• [18]NOOKHAI S,RUXRUNGTHAM K,PHANUPHAK P,et al. Prevalence of CCR2-64I,SDF1-3'A and CCR5-Delta32 alleles in healthy Thais[J]. Eur J Immunogenet,2000,27(3):153-157.
• [19]KAUR G,SINGH P,RAPTHAP CC,et al. Polymorphism in the CCR5 gene promoter and HIV-1 infection in North Indians[J]. Hum Immunol,2007,68(5):454-461.
• [20]YAO Y,SHI L,TAO Y,et al. Distinct HLA allele and haplotype distributions in four ethnic groups of China[J]. Tissue Antigens,2012,80(5):452-461.
• [21]TIAN C,KOSOY R,LEE A,et al. Analysis of East Asia genetic substructure using genome-wide SNP arrays[J]. PLo S One,2008,3(12):e3862.
• [22]XU S,JIN L A. Genome-wide Analysis of admixture in uyghurs and a high-density admixture map for diseasegene discovery[J]. American Journal of Human Genetics,2008,83(3):322-336.
• [23]SHEN Y,CAO D,LI Y,et al. Distribution of HLA-A,-B,and-C alleles and HLA/KIR combinations in Han population in China[J]. J Immunol Res, 2014,2014:565296.
• [24]STEPHENS J,REICH D,GOLDSTEIN D,et al. Dating the origin of the CCR5-Delta32 AIDS-resistance allele by the coalescence of haplotypes[J]. Am J Hum Genet,1998,62(6):1507-1515.
• [25]LALANI A,MASTERS J,ZENG W,et al. Use of chemokine receptors by poxviruses[J]. Science,1999,286(5446):1968-1971.
• [26]DAWSON T,BECK M,KUZIEL W,et al. Contrasting Effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza a virus[J]. Am J Pathol,2000,156(6):1951-1959.
• [27]VOMASKE J,DENTON M,KREKLYWICH C,et al.Cytomegalovirus CC chemokine promotes immune cell migration[J]. J Virol,2012,86(21):11833.
• [28]CARR D,ASH J,LANE T,et al. Abnormal immune response of CCR5-deficient mice to ocular infection with herpes simplex virus type 1[J]. J Gen Virol,2006,87(3):489-499.
• [29]GLASS W,MCDERMOTT D,LIM J,et al. CCR5 deficiency increases risk of symptomatic West Nile virus infection[J]. J Exp Med,2006,203(1):35-40.
• [30]KINDBERG E,MICKIENE A,AX C,et al. A deletion in the chemokine receptor 5(CCR5)gene is associated with tickborne encephalitis[J]. J Infect Dis,2008,197(2):266-269.
• [31]YAO Y,YUE M,ZANG F,et al. Genetic variants in chemokine CC subfamily genes influence hepatitis C virus viral clearance[J]. J Hum Genet,2018,63(7):831-839.
• [32]AHN S,KIM D,CHANG H,et al. Association of genetic variations in CCR5 and its ligand,RANTES with clearance of hepatitis B virus in Korea[J]. J Med Virol,2006,78(12):1564-1571.
• [33]PLATT E J,DURNIN J P,KABAT D Short Communication:HIV-1 variants that use mouse CCR5 reveal critical interactions of gp120's V3 crown with CCR5 extracellular loop 1[J]. AIDS Res Hum Retroviruses,2015,31(10):992-998.
• [34]SILVA E,STUMPF M P. HIV and the CCR5-Delta32 resistance allele[J]. FEMS Microbiol Lett,2004,241(1):1-12.
• [35]BELEW A,MESKAUSKAS A,MUSALGAONKAR S,et al. Ribosomal frameshifting in the CCR5 mRNA is regulated by miRNAs and the NMD pathway[J]. Nature,2014,512(7514):265-269.
• [36]AHLENSTIEL G,BERG T,WOITAS R,et al. Effects of the CCR5-Delta32 mutation on antiviral treatment in chronic hepatitis C[J]. J Hepatol,2003,39(2):245-252.

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