15th Annual Conference of the British HIV Association 1-3 April 2009, Liverpool, UK

ADIPOGENIC GENE VARIANTS IN PATIENTS WITH HIV-ASSOCIATED LIPODYSTROPHY

HIV Med 2009 Apr 1-3 (Suppl 1);15:5 (abstract no. O1)

S Pushpakom¹, A Owen², J Vilar³, D Back² and M Pirmohamed^2
1Royal Liverpool Hospital, Liverpool, UK, ²University of Liverpool, Liverpool, UK, 3North Manchester General Hospital, Manchester, UK

BACKGROUND: Whilst highly active antiretroviral therapy (HAART) has been hugely beneficial in the treatment of HIV, lipodystrophy (LD) associated with HAART is a serious adverse effect, with long term consequences including metabolic disturbances (dyslipidemia, insulin resistance, sometimes leading to diabetes) and an increased risk of ischaemic heart disease. However, LD is clearly related to both the drug regimen and the individual patient and this suggests a role for genetic factors in conferring susceptibility to developing HIV LD. We hypothesised that variation in the genes involved in adipogenesis, and in those implicated in inherited forms of LD, may predispose to the development of LD in HAART-treated patients.

METHODS: DNA samples were obtained from HAART-treated patients with LD (HIV LD+; n=115) or without LD (HIV LD-; n=51) as well as normal presumed HIV-negative healthy controls (n=172). High throughput genotyping utilising Sequenom MALDI-TOF technology was employed to screen 62 SNPs in 10 genes involved in adipogenesis and inherited forms of LD. Statistical analysis was performed using Haploview software to identify single marker and haplotype associations.

RESULTS: SNP markers in two adipogenesis regulators, LPIN1 (P<0.03) and CEBPα (P<0.02), and ZMPSTE24 (P<0.04), a zinc metalloproteinase involved in prelamin A processing, showed significant differences in allele frequencies between HIV LD+ and HIV LD-patients. We also observed significant differences in haplotype frequencies for ZMPSTE24 between these two groups (P<0.05). Multivariate analysis involving all three associated alleles revealed that carriage of more than one associated allele significantly increased the risk of development of LD in HAART-treated patients (P=0.01; OR=2.9).

CONCLUSIONS: Genetic variations in key regulators of adipogenesis could interfere with fat storage and metabolism thereby contributing to the development of LD in HAART-treated HIV patients.

2009-04-01
O1

Copyright © 2009 - British HIV Association (BHIVA) Reproduction of this abstract (other than one copy for personal reference) must be cleared through the BHIVA Organising Secretariat 1 Mountview Court, 310 Friern Barnet Lane, London N20 0LD