IDENTIFICATION OF HUMAN GENETIC LOCI WHICH INFLUENCE SUSCEPTIBILITY TO HIV

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Human DNA polymorphisms are being used in an association analysis among HIV-1-infected hemophiliac and homosexual cohorts to identify susceptibility and resistance genes by searching for distortions in allele frequency, Hardy- Weinberg equilibrium, and linkage equilibrium between different disease categories. The heterogeneity observed in duration of the asymptomatic period and in the rate of CD4 decline may result from cofactors or genetic differences in virulence between HIV variants. However, there is considerable evidence that there is a strong genetic component to infectious disease susceptibility in animal models, but very little is known about the human genetic contribution to viral pathology. A panel of 320 polymorphic loci (200 restriction fragment length polymorphisms and 120 candidate genes) spaced at approximately 10 centiMorgan intervals across all chromosomes are being typed on 1600 patients for distortions of genetic equilibria in an effort to map genes associated with HIV-1 disease progression among different risk categories. Several statistically significant distortions have been observed between dichotomous risk groups and are currently being examined to determine whether these distortions are causally related to disease.