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- aggregation classification "C3".
- aggregation creator B46396.
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- aggregation date "2011".
- aggregation format "application/pdf".
- aggregation hasFormat 3219163.bibtex.
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- aggregation language "eng".
- aggregation rights "I have retained and own the full copyright for this publication".
- aggregation subject "Biology and Life Sciences".
- aggregation title "Comprehensive characterization of LEDGF/p75 in a HIV-1-infected patient cohort".
- aggregation abstract "BACKGROUND: Lens epithelium derived growth factor/transcriptional co-activator p75 (LEDGF/p75) is an important cellular co-factor for the HIV enzyme integrase. In the present study, we evaluated if genetic variation in the LEDGF/p75 gene and mRNA expression levels might explain differences in HIV disease progression. METHODS: Samples were derived from a therapy-naïve patient cohort from the Ghent University Hospital and from the long-term-non-progressor patient Spanish RIS cohort. A comprehensive genomic scan of the coding region and 3’UTR of LEDGF/p75 was performed using high resolution melting curve analysis and Sanger sequencing to identify single nucleotide polymorphisms (SNPS). In addition, LEDGF/p75 mRNA expression levels were determined from patient PBMCs using RT-qPCR with validated reference genes for normalization. RESULTS: In total 325 patient samples were investigated, of which 291 (90%) of Caucasian and 34 (10%) of African origin, and among which a large group of Elite controllers (n=49) and Viremic controllers (n=62). In these samples, 24 SNPs were analyzed, including 5 in the coding region (2 synonymous and 3 non-synonymous), 17 in the flanking non-coding regions and in the 3’UTR, and two additional tagSNPs as described by Madlala et al. (Aids, 2011) in two South African cohorts. One SNP in the 3’UTR region (rs2737835, n=46) had a higher representation in Caucasian Elite controllers and was correlated with lower LEDGF/p75 mRNA levels (P=0.047) and with a slower CD4 decline (P= 0.042). rs2737828 (n=13) was under-represented in Caucasian HIV patients and linked to lower LEDGF/p75 expression (P=0.013). The presence of intron SNP (rs16933270, n=6) was associated with a slower CD4 decline in African patients (P=0.017), and this CD4 decline was comparable with that of African slow disease progressors. Interestingly, the presence of one tagSNP (rs12339417, n=95) was significantly correlated with a decreased viral load, but in contrast to the results of Madlala et al. (Aids, 2011), this SNP was not correlated with the CD4 slope and neither with LEDGF/p75 mRNA levels. CONCLUSIONS: Although the data of the present investigation was not entirely comparable with the results of Madlala et al. (Aids, 2011), our data supports their hypothesis that host factors influence HIV disease progression. The observed differences between the European and South African cohorts may be of ethnical origin, or due to different infection phases. In the investigated cohorts, two SNPs were associated with lower LEDGF/p75 mRNA expression in Caucasians, and one SNP was associated with slower disease progression in Africans. The significant correlation with the tagSNP (rs12339417) and the decreased viral load is surprising as this was not correlated with a delayed CD4 decline, nor with LEDGF/p75 expression. This might indicate that either conformational changes or factors upstream of mRNA transcription might influence the action of LEDGF/p75 in these HIV patients.".
- aggregation authorList BK117153.
- aggregation aggregates 3219174.
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