A single-nucleotide polymorphism in the sterol-regulatory element-binding protein 1c gene is predictive of HIV-related hyperlipoproteinaemia

• Published in: AIDS (London) Vol. 15; no. 15; pp. 2045 - 2049
• Main Authors: MISEREZ, André R, MULLER, Patrick Y, BARELLA, Luca, SCHWIETERT, Martin, ERB, Peter, VERNAZZA, Pietro L, BATTEGAY, Manuel
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 19.10.2001
• Subjects: Antiretroviral Therapy, Highly Active - adverse effects; Apolipoproteins E - genetics; Biological and medical sciences; CCAAT-Enhancer-Binding Proteins - genetics; CD4 Lymphocyte Count; Cohort Studies; DNA-Binding Proteins - genetics; Drug toxicity and drugs side effects treatment; highly active antiretroviral therapy; HIV Infections - complications; HIV Infections - drug therapy; HIV-1 - physiology; Human immunodeficiency virus; Humans; Hyperlipoproteinemias - genetics; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Pharmacology. Drug treatments; Polymorphism, Single Nucleotide - genetics; Predictive Value of Tests; RNA, Viral - blood; SREBP-1c protein; Sterol Regulatory Element Binding Protein 1; Transcription Factors; Pathogenesis; Toxicity; Lipids; Hyperlipoproteinemia; Lipoprotein; Homozygosity; Genetic determinism; Binding protein; Messenger RNA; Gene; Antiviral; Dyslipemia; Mechanism of action; Human; Immunopathology; Pharmacogenetics; Metabolic diseases; Genotype; AIDS; Immune deficiency; Infection; Viral disease; Aminoacid; Nucleotide; Mutation; Predictive factor; Polymorphism
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-200110190-00020

A single-nucleotide polymorphism (3'322C/G) was identified in the gene encoding a key cholesterol/triglyceride regulator, sterol-regulatory element-binding protein 1c (SREBP-1c). Although it did not alter the amino acid sequence, SREBP-1c-3'322C/G was predictive of highly active antiretroviral therapy-related hyperlipoproteinaemia. Increases in cholesterol were less frequently associated with homozygous SREBP-1c-3'322G (genotype 22) than with heterozygous/homozygous SREBP-1c-3'322C (genotypes 11/12) and correlated with leptin and insulin increases, particularly in genotype 11/12 carriers. A functional mutation linked to SREBP-1c-3'322C/G or messenger RNA conformation differences may explain our findings.