Population Survey of CCR5 Δ32, 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

Abstract

The aim of this study is to determine in indigenous Chinese ethnic groups the frequencies of the chemokine (SDF1 3'A) and chemokine receptors (CCR5 delta32, CCR5 m303, and CCR2b 64I) HIV-1/AIDS restriction alleles. The study includes two cohorts; the first comprised 3165 indigenous healthy subjects representing eight ethnic groups: Han (n = 1406), Uygur (n = 316), Mongolia (n = 134), Hui (n = 386), Tibetan (n = 330), Zhuang (n = 378), Dai (n = 101), and Jingbo (n =114). The second cohort consisted of 330 HIV-1-infected (86 subjects infected by sexual transmission and 198 subjects infected by HIV-1-contaminated blood or by sharing injection equipment; the remaining 46 subjects said nothing about HIV-1 transmission) and 474 HIV-1-uninfected Han Chinese belonging to one of two HIV-1 high-risk groups: intravenous drug users (n = 215) and individuals with sexually transmitted diseases (n = 259). Genotypes for the four genes were obtained using PCR (CCR5 delta32) or PCR-restriction fragment length polymorphism. Randomly selected amplified PCR products were further confirmed by direct DNA sequencing. The variant allele frequencies were determined to be 0% to 3.48% for CCR5 delta32, 0% for CCR5 m303, 16.23% to 28.79% for CCR2b 64I, and 17.70% to 27.76% for SDF1 3'A in Chinese healthy individuals from eight ethnic groups. These findings show that allele frequencies differ among the eight Chinese ethnic groups for CCR5 delta32, CCR2b 64I, and SDF1 3'A and that the CCR5 m303 and CCR5 delta32 mutant alleles were absent or infrequent in Chinese, which may be helpful for studies of specific anti-HIV-1 vaccine trials and coreceptor inhibitor drug targets in Chinese populations. Furthermore, we observed no significant differences in allele or genotypic frequencies between HIV-1-infected and HIV-1-uninfected groups from the Han ethnic group. Our finding is the first reporting that there is likely no effect of the examined polymorphisms in our study on HIV-1 transmission in the Chinese Han population, However, the genetic effects of these and other AIDS-modifying polymorphisms on the pathogenesis and clinical outcome of HIV-1/AIDS diseases is under investigation in Chinese populations.

Global human genetics of HIV-1 infection and China

“…Heterozygous CCR5-32 genotypes were found in 3 out of 1254 Han Chinese, with an allele frequency of 0.00119. Findings from this study and others [88,89] show that CCR5-32 mutants do occur in Chinese population (all are individuals with heterozygous CCR5-32), and can be inherited at a very low frequency [87][88][89].…”

“…The polymorphism demonstrates a decreasing north-south cline across Eurasia and is largely absent in African, Asian and Oceanic populations [84][85][86], interestingly this distribution may have become fixed 700 years ago in northwestern Europe [86]. Indeed, studies to date indicate that CCR5-32 mutant alleles were absent or infrequent in Chinese [87][88][89][90][91][92][93]. Homozygous genotypes have not been identified in Chinese populations, while heterozygous CCR5-32 is extremely rare or absent in most Chinese populations studied [87][88][89][90][91][92][93].…”

“…The frequencies of heterozygous and homozygous CCR2-64I in Chinese were 13-35% and 1-8%, respectively, varying from study to study [87][88][89][90][91][92][93]. There is no difference in the frequencies of both heterozygous and homozygous CCR2-64I between HIV-1 infected and HIV seronegative individuals, suggesting no association of CCR2-64I with HIV-1 transmission in Chinese.…”

“…Wang et al in collaboration with us [87] conducted a large scale investigation on human genetic polymorphisms in three cohorts of Chinese: 1) 3165 indigenous healthy subjects representing eight ethnic groups: Han (n = 1406), Uygur (n = 316), Mongolia (n = 134), Hui (n = 386), Tibetan (n = 330), Zhuang (n = 378), Dai (n = 101), and Jingbo (n =114); 2) 330 HIV-1 infected (86 subjects infected by sexual transmission and 198 subjects infected by HIV-1 contaminated blood or by sharing injection equipment; the remaining 46 subjects said nothing about HIV-1 transmission); and 3) 474 HIV-1 uninfected Han Chinese belonging to one of two HIV-1 high-risk groups: intravenous drug users (n = 215) and individuals with sexually transmitted diseases (n = 259). Heterozygous CCR5-32 genotypes were found in 3 out of 1254 Han Chinese, with an allele frequency of 0.00119.…”

“…Indeed, studies to date indicate that CCR5-32 mutant alleles were absent or infrequent in Chinese [87][88][89][90][91][92][93]. Homozygous genotypes have not been identified in Chinese populations, while heterozygous CCR5-32 is extremely rare or absent in most Chinese populations studied [87][88][89][90][91][92][93]. There is no evidence that CCR5-32 influences the HIV-1 transmission or epidemic in China.…”