A 32-bp deletion on the CCR5 gene (ccr5delta32) co

A 32-bp deletion on the CCR5 gene (ccr5delta32) confers resistance to HIV-1 infection. This deletion is common in Caucasians, but rare in Asians. Since the frequency of the ccr5delta32 allele of Chinese in mainland China has been unknown we investigated the ccr5delta32 mutation in a cohort of 407 Chinese people in this area. A 225-bp fragment of CCR5 encompassing the 32-bp region was analysed by PCR, hybridization and sequencing. Only 1 out of 407 subjects was heterozygous for ccr5delta32 and no homozygotes were detected. The frequency of ccr5delta32 in this cohort is thus 0.00123, i.e. much lower than that of Caucasians. The ccr5delta32 heterozygote is a healthy young man. To our knowledge this is the first ccr5delta32 mutant found in Chinese people. The results indicate that ccr5delta32 does exist in Chinese people, but at very low frequency. This suggests that ccr5delta32 is not a significant factor for the genetic resistance to HIV-1 in Chinese people.

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Background: A 32-base pair (bp) deletion mutation in the beta-chemokine receptor CCR5 gene has been associated with resistance against human immunodeficiency virus type 1 (HIV-1) infection and disease. Large-scale studies conducted among Caucasians indicate that individuals who are homozygous for this deletion mutation (D32/D32) are protected against HIV-1 infection despite multiple high-risk exposures, whereas CCR5/ D32 heterozygotes have a slower progression to acquired immunodeficiency syndrome (AIDS).

Objective: To determine the genotype and allele frequencies of the CCR5 gene 32-bp deletion mutation among ethnically diverse non-Caucasian populations.

Methods: DNA, extracted from blood collected between 1980 and 1997 from 1912 individuals belonging to various ethnic groups, including 363 Caucasians, 303 Puerto Rican Hispanics, 150 Africans, 606 Asians, and 490 Pacific Islanders, were analyzed for the CCR5 gene 32-bp deletion mutation by a polymerase chain reaction (PCR)-based assay, using an oligonucleotide primer pair designed to discriminate CCR5 alleles without restriction endonuclease analysis.

Results: The comparative frequency of CCR5/D32 heterozygosity was 61 of 363 (16. 8%) in Caucasians, 17 of 303 (5.6%) in Puerto Rican Hispanics, 9 of 490 (1.8%) in Pacific Islanders, 0 of 606 (0%) in Asians, and 0 of 150 (0%) in Africans.

Conclusions: The data confirm the high frequency of CCR5/D32 heterozygosity among Caucasians. Intermediate and low-level D32 allele frequencies among Puerto Rican Hispanics and Hawaiians could be attributed to recent European Caucasian gene flow. By contrast, the inability to detect the D32 allele among Asians and other Pacific Islander groups suggests that other mechanisms are responsible for resistance to HIV-1 infection in these populations.



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Chemokine CC receptor type 5 (CCR5) is a cell surface receptor that has high affinity for chemotropic cytokines called chemokines. The CCR5 gene contains a 32 base pairs (bp) deletion (CCR5Δ32). This deletion may result in a malformed and nonfunctional receptor, reported to be responsible for the development and dissemination of different cancers. CCR5Δ32 exists in two allelic forms i.e. deletion (D) and wild type (WT). This study aims to detect the role of CCR5Δ32 in breast cancer development. Blood samples were collected from breast cancer patients (330) and controls of same gender (306). Along with this histopathologically diagnosed malignant tissue samples were also excised from breast lesions of 100 patients. Genetic variations within the blood and tissue samples were examined by PCR then observed through gel electrophoresis and confirmed by direct DNA sequencing. Obtained DNA sequences were aligned and analyzed by MEGA6 software. Genotypic and association analyses were done by SPSS software version 17.0. Deletion of 32 bp in CCR5 gene has been analyzed. Genotypic variations of CCR5Δ32 are; homozygous wild type (WT/WT), heterozygous deletion (WT/D) and homozygous deletion (D/D). Statistical analyses of CCR5Δ32 data revealed that WT/D was significantly higher in blood samples of breast cancer patients (7.27% (24/330)) as compare to controls (1.30% (4/306)). In tumor tissue samples WT/WT being the most frequent genotype (99.00% (99/100)) with 1.00 (1/100) of D/D which suggested that it may be acquired. Hence, association analysis showed that CCR5Δ32 is positively associated with breast cancer in Pakistan (p < 0.001). The risk ratio of CCR5Δ32 was 5.6610 (95% confidence interval: 2.0377 to 15.7267) and odds ratio was calculated to be 6.0335 (95% confidence interval: 2.1288 to 17.0999) which signifies that deletion also increases the risk of breast cancer development. Moreover, association analyses also revealed that clinicopathological features do not have any impact on the CCR5Δ32 genotype of breast cancer. This suggests that deletion of 32 bp in CCR5 gene may be associated with breast cancer. CCR5 signals the activation and migration of immune cells at the site of tumor formation. Because of deletion; deformed CCR5 receptor might be unable to express and function properly which may subdue the immunity against cancer hence, leading to its progression.


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