Rs2395029

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: spittoon 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]

nature Abacavir hypersensitivity rs2395029

[PMID 18369459] rs2395029 reported to be associated with psoriasis in a large US/UK study

[PMID 19115949] HIV-1 nonprogressors (odds ratio, 3.47)

Marker HLA-B*5701 hypersensitivity to the HIV drug abacavir; FDA warning here

GWAS snp
PMID	[PMID 20041166]
Trait	HIV-1 control
Title	Common Genetic Variation and the Control of HIV-1 in Human
Risk Allele
P-val	1E-11
Odds Ratio	NR NR

GWAS snp
PMID	[PMID 21051598]
Trait
Title	The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation
Risk Allele	G
P-val	1E-25
Odds Ratio	5.3000 [NR]