Global survey of genetic variation in CCR5 , RANTES , and MIP-1 α: Impact on the epidemiology of the HIV-1 pandemic

• DOI: 10.1073/pnas.091056898
• Publication Date: 2002-07-26T14:37:36Z
• Authors: Enrique Gonzalez; Rahul Dhanda; Mike Bamshad; Srinivas Mummidi; Reni Geevarghese; Gabriel Catano; Stephanie A. Ande...; Elizabeth A. Walter; Kevin T. Stephan; Michael F. Hammer; Andrea Mangano; Luisa Sen; Robert A. Clark; Seema S. Ahuja; Matthew J. Dolan; Sunil K. Ahuja
• Keywords: Chemokine receptor CCR5; Pandemic

Expression of CC chemokine receptor 5 (CCR5), the major coreceptor for HIV-1 cell entry, and its ligands (e.g., RANTES MIP-1α) is widely regarded as central to pathogenesis infection. By surveying nearly 3,000 HIV+ HIV− individuals from worldwide populations polymorphisms in genes encoding RANTES, MIP-1α, CCR5, we show that evolutionary histories human have had a significant impact on distribution variation these genes, this may be responsible, part, heterogeneous nature epidemiology pandemic. The varied haplotypes (AC, GC, AG) associated with population-specific transmission- disease-modifying effects striking example. Homozygosity AC haplotype was an increased risk acquiring well accelerated disease progression European Americans, but not African Americans. Yet, prevalence ancestral high origin, substantially lower non-Africans. In Japanese cohort, AG-containing pairs were delay progression; however, now their contribution other parts world negligible because AG infrequent non-Far East Asians. Thus, , MIP-1 α, CCR5 phenotypic susceptibility results complex pattern biological determinants epidemiology. These findings important implications design, assessment, implementation effective intervention prevention strategies.