title: Distribution of human chemokine (C-X3-C) receptor 1 (CX3CR1) gene polymorphisms and haplotypes of the CC chemokine receptor 5 (CCR5) promoter in Chinese people, and the effects of CCR5 haplotypes on CCR5 expression.
abstract: Two chemokine (C-X3-C) receptor 1 (CX3CR1) gene polymorphisms, V249I and T280M, and 10 CC chemokine receptor 5 (CCR5) promoter haplotypes, P1-P10, have recently been reported to influence the progression of acquired immune-deficiency syndrome (AIDS). As these studies were performed mainly with Caucasian and African-American subjects, we determined the distribution of these alleles in Chinese people for the purpose of predicting possible clinical responses to the human immunodeficiency virus type 1 (HIV) epidemics in countries with significant Chinese populations, as well as to establish their effects on the expression of surface CCR5. Ninety-six HIV-negative Chinese individuals in Taiwan were subjected to genotyping, and we thus determined that the allelic frequencies of CX3CR1V249I and T280M changes were 2.6% and 2.1%, respectively, which were lower than found in Caucasians (25.5% and 14.0%, respectively). Unlike the previous reports, we only detected CCR5P1 and P4 haplotypes in Taiwanese people, and the P1/P1, P1/P4 and P4/P4 genotype frequencies were 21.0%, 41.1% and 37.9%, respectively. The sequencing data confirmed the results of previous studies, showing that CCR5P1 exhibited a complete linkage disequilibrium with a polymorphic allele 59029A present in the CCR5 promoter. Furthermore, fluorescence-activated cell sorter analysis revealed that, in the absence of the CCR2-64I mutation, individuals carrying CCR5P1 tended to express more surface CCR5 on monocytes and CD4+ cells. Therefore, this study not only reports the frequencies for the CX3CR1 and CCR5 promoter haplotypes in a Chinese population living in Taiwan, but also identifies a statistical link between the P1/P1 haplotype and the elevated CCR5 expression levels in the study group.
authors.affiliation: Department of Microbiology-Immunology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: S C
authors.initials: SC
authors.lastname: Lu
authors.forename: P S
authors.initials: PS
authors.lastname: Hsieh
authors.forename: Y H
authors.initials: YH
authors.lastname: Huang
authors.forename: H I
authors.initials: HI
authors.lastname: Huang
authors.forename: T H
authors.initials: TH
authors.lastname: Ying
authors.forename: B
authors.initials: B
authors.lastname: Shieh
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D000073883:CX3C Chemokine Receptor 1; D002681:China; D005260:Female; D005787:Gene Frequency; D015658:HIV Infections / Q000208:ethnology / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics* / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D008565:Membrane Proteins; D019713:Receptors, CCR5; D019707:Receptors, Chemokine