Background:  Single-nucleotide polymorphysms in genes involved in apoptosis and in adipocye metabolism may explain why lipoatrophy occurs in some, but not all, ART-treated individuals. The present study aims at evaluating the influence of FASl-670 and APOC3 polymorphisms on ART-associated lipoatrophy.

Methods:  We included in the study 274 patients on ART who were enrolled in Lipo.I.Co.N.A. We assessed the distribution of FAS-670 and APOC3-455 polymorphisms and calculated crude and adjusted relative rates  of lipoatrophy (time of the first observed fat loss at any site) using Poisson regression.

Results:  In our population, 23.3% were female and 36.1% hepatitis C virus (HCV)⁺; 21.1% of the person-year follow-up was spent on non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimen and 42.1% on protease inhibitor (PI); 47.3% was spent on zidovudine/stavudine (AZT/3TC), 20.5% on lamivudine/stavudine (d4t/3TC), and 16.4% on didanosine/stavudine (ddI/d4T). During 778 person-years’ follow-up, we observed 55 lipoatrophy events, crude incidence rate 70.7 (54.2 to 92.0) per 1000 person-years follow-up. The distribution of FASL-670 was:  AA 95 (35%), AG 113 (41%), and GG 66 (24%); of APOC3, ut was:  CT 129 (47%), TT 107 (39%), and CC 38 (14%). After having adjusted for gender, HIV exposure, age, current viral load, HCV serology, NRTI pair/“third drugs” currently used, and months of pre-HAART exposure to NRTI, the relative rate of lipoatrophy comparing APOC3 CT with CC genotypes was 6.3 (95%CI 1.4 to 28.0, p = 0.014) while FASL-670 AG compared with AA was protective against lipoatrophy (RR 0.34, 95%CI 0.15 to 0.76, p = 0.009). Patients on d4T/3TC were at higher risk of lipoatrophy than those on AZT/3TC (adjusted RR 2.79, 95%IC 1.23 to 6.29, p = 0.013). The risk associated with the most unfavorable genetic scenario (overall adjusted RR for APOC3 CT combined with FASL670 = AA vs other possible combinations = 2.28 95%CI 1.13 to 4.57, p = 0.019) was not different in patients currently on d4T/3TC (RR = 3.25, 95%CI 0.95 to 11.1) or on another pair of NRTI (1.95, 95%CI 0.82 to 4.59, for the interaction p = 0.44) after having adjusted for other potential confounders (the same listed above). 

Conclusions:  Our study suggests that FAS genotype -670 AG is protective against lipoatrophy compared with the AA genotype, while patients with APOC3 genotype CT are at higher risk. Our results confirm previous observations linking nucleoside analogues, particularly d4T, to the emergence of lipoatrophy, even if there is no evidence of a greater detrimental effect on patients with an unfavorable genetic asset. The determination of APOC3 and FAS polymorphisms, a relatively simple and inexpensive assay, could be considered to identify patients at potentially higher risk of lipoatrophy.