Short Communication doi: 10.1111/j.1744-313X.2007.00667.x © 2007 The Authors Journal compilation © 2007 Blackwell Publishing Ltd, International Journal of Immunogenetics 34, 153–156 153 Blackwell Publishing Ltd Distribution of CCR2 polymorphism in HIV-1-infected and healthy subjects in North India G. Kaur,* P. Singh,* N. Kumar,* C. C. Rapthap,* G. Sharma,* M. Vajpayee,† N. Wig,‡ S. K. Sharma‡ & N. K. Mehra* Summary Substitution of V64I in CCR2 relates to delayed pro- gression to AIDS and protects against HIV-1 infection. We examined the distribution of V64I in HIV-infected and healthy North Indian subjects. No significant difference in the allele or genotype distribution of CCR2 V64I polymorphism was observed, indicating that there is no association between CCR2 V64I polymorphism and sus- ceptibility to HIV infection in North Indian population. Inter-individual variability in the rate of disease progres- sion from initial infection with HIV to appearance of AIDS is well known. People infected with this virus have inherent heterogeneity in the innate, humoral and cell- mediated immune responses as well as their response to antiretroviral treatment. It has been shown that genetic polymorphisms in chemokine receptors CCR2 and CCR5 play an important role in HIV infection and disease progression (Smith et al., 1997; McNicholl et al., 2003; Libert et al., 1999; O’Brien et al., 2000; Christine et al., 2001; Carrington et al., 2001; O’Brien & Nelson, 2004; Kaslow et al., 2005; Shrestha et al., 2006; Arenzana- Seisdedos & Parmentier, 2006). Particularly, a valine to isoleucine substitution at position 64 within the first trans- membrane region of CCR2 has been associated with delayed disease progression to AIDS, about 2–4 years later than homozygous individuals carrying the wild-type allele (Smith et al., 1997; Kostrikis et al., 1998; Anzala et al., 1998; Ioannidis et al., 2001; Dean et al., 2002; Mulherin et al., 2003). Louisirirotchanakul et al. (2002) have reported that CCR2 64I homozygosity is associated with a reduced risk of acquiring infection among the HIV-1 discordant couples in Thailand. The 64I allele occurs at a population frequency of 8 –10% among Caucasians (Smith et al., 1997; Easterbrook et al., 1999; Clark et al., 2001), 15– 17% among subjects of African origin (Smith et al., 1997; Clark et al., 2001) and 20.6% in the Chinese populations (Zhang et al., 2006). The mechanism of CCR2 64I protective effect remains largely unknown. However, it has been suggested that since the gene is in close proximity to CCR5 on chromosome 3p21.3 (Samson et al., 1996), the mutation could be strongly linked to other disease modifying mutation(s) in the CCR5 promoter region (McDermott et al., 1998; Martin et al., 1998; Gonzalez et al., 1999; Carrington et al., 1999; Salkowitz et al., 2003; Hladik et al., 2005). Alternatively, it has been suggested that this polymorphism affects stability of CCR2A isoform molecules that bind to CCR5 in the cytoplasm and down-regulate its surface expression resulting in delay in disease progression in patients with this allele (Nakayama et al., 2004). Another report has indicated that CCR2 64I protein can preferentially dimerize with CXCR4 polypeptides (Mellado et al., 1999) and might affect its cell surface expression. As the prevalence of CCR2 V64I polymorphism has not been fully explored in the Asian Indian population, the current study was undertaken to examine the relation- ship between CCR2 polymorphism and status of HIV infection. A total of 221 random healthy individuals and 180 HIV seropositive subjects of same ethnicity from Northern India (particularly Delhi and its immediate surrounding areas) were enrolled in the study. The infected cohort was collected from the AIDS clinic of the All India Institute of Medical Sciences (AIIMS), New Delhi, and consisted of chronically infected individuals with confirmed serodiagnosis and no prior history of antiretroviral therapy. The seropositive subjects had a median age of 31 years while their median CD4 counts were 198 per μL (range 23–1284 per μL) and median CD8 counts were 937 per μL (range 192–6948 per μL). These subjects were in different stages of disease progression. Depending on their CD4 counts and based on clinical symptoms (Table 1) they were divided into clinical categories A (n = 50), B (n = 59) and C (n = 71) as per the revised Centers for Disease Control and Prevention (CDC) classification system (CDC, 1993; Vajpayee et al., Departments of * Transplant Immunology and Immunogenetics, † Microbiology and ‡ Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India Received 6 December 2006; accepted 27 December 2006 Correspondence: N. K. Mehra, Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India. Tel: +91 11 2658 8588; Fax: +91 11 2658 8663; E-mail: narin98@hotmail.com