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rs2395029 is a SNP in the major histocompatibility complex (MHC) region, and several studies have shown that the rs2395029(G) allele is 99.9% predictive of the presence of an HLA-B*5701 allele. This HLA allele, in turn, has been associated with several conditions.
A study of 51 cases of flucloxacillin drug-induced liver injury (DILI), an important cause of serious liver disease, along with a replication study of another 23 cases, found that the rs2395029(G) carriers were at highly increased risk (odds ratio 80, p=8.7x10(-33)).[PMID 19483685]
- see also: 23andMe blog rs2395029(G;G) increases the odds of drug-induced liver injury in response to flucloxacillin by 45x
[PMID 17641165] This SNP is thought to be involved in determining the HIV viral load set point during the asymptomatic period of infection. This SNP is estimated to explain 9.6% of the total variation in the viral set point.
Humans show remarkable variation in vulnerability to infection by HIV-1 and especially in the clinical outcome following infection. One striking and largely unexplained difference is the level of circulating virus in the plasma during the non-symptomatic phase preceding progression to AIDS. This is known as the viral set point and can vary among individuals by as much as 4 to 5 logs.
The HCP5 (HLA complex P5) gene is located 100 kb centromeric from HLAB on chromosome 6. HCP5 is a good candidate to interact with HIV-1, possibly through an antisense mechanism. Moreover, HCP5 is predicted to encode two proteins, and the associated polymorphism results in an amino acid substitution in one of these.
rs9264942 is also reported to be associated with reduced HIV viral load set point.
In European populations, the rs2395029(G) allele is in tight linkage disequilibrium (r2 = 1) with the HLA-B*5701 allele, and therefore is predictive of hypersensitivity to the drug abacavir, an antiviral used to treat HIV+ individuals.[PMID 18684101]
[PMID 24270849] rs2395029 was found to be associated with psoriasis based on a study by the eMERGE network in which electronic medical records were searched to find clinical associations associated with selected SNPs.
|Title||Common Genetic Variation and the Control of HIV-1 in Human|
|Odds Ratio||NR NR|
|Title||The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation|
|Odds Ratio||5.3000 [NR]|
[PMID 18256235] WGAViewer: software for genomic annotation of whole genome association studies.
[PMID 18982067] HIV-1 disease-influencing effects associated with ZNRD1, HCP5 and HLA-C alleles are attributable mainly to either HLA-A10 or HLA-B*57 alleles.
[PMID 19050382] Association of HLA-C and HCP5 gene regions with the clinical course of HIV-1 infection.
[PMID 19107206] Distinct genetic loci control plasma HIV-RNA and cellular HIV-DNA levels in HIV-1 infection: the ANRS Genome Wide Association 01 study.
[PMID 19182814] New insights into the pathogenesis and genetics of psoriatic arthritis.
[PMID 19276793] Host genetics and HIV-1 viral load set-point in African-Americans.
[PMID 19474294] Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
[PMID 19679225] X chromosomal variation is associated with slow progression to AIDS in HIV-1-infected women.
[PMID 19935381] A polymorphism in the HCP5 gene associated with HLA-B*5701 does not restrict HIV-1 in vitro.
[PMID 20487506] A whole genome association study of mother-to-child transmission of HIV in Malawi.
[PMID 20534626] Use of the HCP5 single nucleotide polymorphism to predict hypersensitivity reactions to abacavir: correlation with HLA-B*5701.
[PMID 20552027] Host and viral genetic correlates of clinical definitions of HIV-1 disease progression.
[PMID 21107268] Screening low-frequency SNPS from genome-wide association study reveals a new risk allele for progression to AIDS.
[PMID 21221856] The search for host genetic factors of HIV/AIDS pathogenesis in the post-genome era: progress to date and new avenues for discovery.
[PMID 21253569] Genome-wide association study SNPs in the human genome diversity project populations: does selection affect unlinked SNPs with shared trait associations?
[PMID 21514285] Rapid HCP5 single-nucleotide polymorphism genotyping: a simple allele-specific PCR method for prediction of hypersensitivity reaction to Abacavir.
[PMID 21854194] Distribution of polymorphisms in cytochrome P450 2B6, histocompatibility complex P5, chemokine coreceptor 5, and interleukin 28B genes in inhabitants from the central area of Argentina.
[PMID 21860345] Rising HIV-1 viral load set point at a population level coincides with a fading impact of host genetic factors on HIV-1 control.
[PMID 22474614] Host Genes Important to HIV Replication and Evolution.
|qualified_impact||Insufficiently evaluated pathogenic|
|summary||GWAS association with AIDS progression.|
[PMID 23403273] Novel genetic association of TNF-alpha-238 and PDCD1-7209 polymorphisms with long-term non-progressive HIV-1 infection.
[PMID 24861233] Development of multiplex pyrosequencing for HLA-B*57:01 screening using single nucleotide polymorphism haplotype