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

Int J Immunogenet. 2005 Apr;32(2):99-106. doi: 10.1111/j.1744-313X.2005.00498.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Asian People / genetics*
  • CX3C Chemokine Receptor 1
  • China
  • Female
  • Gene Frequency
  • HIV Infections / ethnology
  • HIV Infections / genetics
  • Haplotypes
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics
  • Receptors, CCR5 / genetics*
  • Receptors, CCR5 / metabolism
  • Receptors, Chemokine / genetics*
  • White People / genetics

Substances

  • CX3C Chemokine Receptor 1
  • CX3CR1 protein, human
  • Membrane Proteins
  • Receptors, CCR5
  • Receptors, Chemokine