Factors impacting the expression of membrane-bound proteins in lymphocytes from HIV-positive subjects

Chandler, Becky; Detsika, Maria G.; Khoo, Saye; Williams, J.; Back, David; Owen, Andrew

doi:10.1093/jac/dkm230

Cited by 18 publications

(21 citation statements)

References 18 publications

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“…A study reported that the expression of ABCB1 gene in lymphocytes extracted from HIV-positive patients was significantly greater in males relative to females, using GAPDH as an endogenous control with a male to female expression ratio of 1.34-fold (Chandler et al, 2007). However, the present findings suggest that GAPDH should not be used as a singleendogenous control for normalization of ABCB1 gene expression in PBMCs.…”

Section: Evaluation Of Housekeeping Gene Stabilitycontrasting

confidence: 67%

“…Recently, it was found that P-gp expression in intestine and liver does not correlate with its expression in PBMCs (Albermann et al, 2005). A study reported that males have greater expression levels of ABCB1 in peripheral lymphocytes compared with females, approximately 1.3-fold, using glyceraldehyde-3P dehydrogenase (GAPDH) as an endogenous control gene for normalization (Chandler et al, 2007). However, another study concluded that beta-2 microglobulin (β-2M) is a more stably expressed endogenous control gene and should be used for normalization of the expression levels in lymphocytes, rather than GAPDH or beta-actin (actin-β), and that more than one gene should be used for normalization (Vandesompele et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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ABCB1 gene expression in peripheral blood mononuclear cells in healthy Thai males and females

Sudchada

Oo-puthinan²,

O³

et al. 2010

Genet. Mol. Res.

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ABSTRACT. We compared the expression of the ABCB1 gene in healthy male and female Thai subjects; this gene encodes the P-glycoprotein transporter in peripheral blood mononuclear cells (PBMCs). We also identified the most suitable housekeeping genes for normalization of ABCB1 expression levels in PBMCs. PBMCs from 30 females and 26 males were isolated. Total RNA was extracted, followed by reverse transcription (100 ng total RNA per sample). The internal normalization controls were actin-β, β-2M and GAPDH. Real-time quantitative PCR was then performed to determine the expression levels of the ABCB1 gene. The expression levels were found to be 1.5-to 2.5-fold higher in males, depending on the endogenous control used for normalization. Actin-β was the most stable control gene and could be used as a single endogenous control for normalization of ABCB1 expression levels in PBMCs. However, more than one endogenous control genes are recommended for normalization of gene expression. We conclude that the expression levels of ABCB1 in PBMCs is influenced by gender; this helps, in part, explain the gender difference in pharmacokinetics and pharmacodynamics of drugs that are P-glycoprotein substrates. ABCB1 gene expression profiles need to be carefully interpreted with regards to the endogenous control genes that are involved.

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Section: Evaluation Of Housekeeping Gene Stabilitycontrasting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

ABCB1 gene expression in peripheral blood mononuclear cells in healthy Thai males and females

Sudchada

Oo-puthinan²,

O³

et al. 2010

Genet. Mol. Res.

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“…It was reported that P-glycoprotein expression in human liver [32] and lymphocytes [33] was lower in females than in males, possibly due to the effects of estradiol and progesterone on P-glycoprotein expression [13]. Therefore, these sex hormones may contribute to the sex specificity in the effect of the MDR1 polymorphism on interpersonal sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Implication of P-Glycoprotein in Formation of Depression-Prone Personality: Association Study between the C3435T <b><i>MDR1</i></b> Gene Polymorphism and Interpersonal Sensitivity

Enokido¹,

Suzuki²,

Sadahiro³

et al. 2014

Neuropsychobiology

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Background and Aim: Interpersonal sensitivity is defined as undue and excessive awareness of, and sensitivity to, the behavior and feelings of others. Previous studies suggested that interpersonal sensitivity is one of the vulnerable factors to depression, and that genetic factors and cortisol are involved in the formation of interpersonal sensitivity. On the other hand, P-glycoprotein, which is encoded by the multidrug resistance 1 (MDR1) gene, serves as a barrier to entry and as an active eliminator for xenobiotics and cellular metabolites including cortisol, which is implicated in multiple brain functions. In the present study, we examined the effects of the MDR1 C3435T polymorphism (rs1045642) on interpersonal sensitivity in healthy subjects. Methods: The subjects were 842 healthy Japanese volunteers (mean age = 26.7 years, male/female ratio = 490/352). The C3435T polymorphism of MDR1 gene was detected by a PCR method, and interpersonal sensitivity was assessed by the Interpersonal Sensitivity Measure (IPSM). Results: The 2-factor analysis of covariance (ANCOVA) showed a significant main effect of the MDR1 genotype on the IPSM scores with a significant interaction between the genotype and gender. The subsequent 1-factor ANCOVA showed that in females the C/C genotype group had higher IPSM scores than the C/T genotype group (p < 0.001) and the T/T genotype group (p < 0.001), and the C/T genotype group had higher IPSM scores than the T/T genotype group (p = 0.014). In males no significant association was found between the MDR1 genotype and the IPSM scores. In allelic analyses using the χ² tests, the C allele frequency in females was significantly higher (p < 0.001) in the high IPSM group than in the low IPSM group, while there was no significant difference in the C allele frequency between the high and low IPSM groups in total subjects and males. Conclusion: The present study suggests that the C3435T polymorphism of the MDR1 gene affects the formation of a depression-prone personality trait in Japanese females.

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“…Its expression in the endothelium of the blood-brain barrier prevents the entry of possibly toxic compounds into the brain [14,17]. Besides its expression in barrier tissues, P-glycoprotein is expressed in single cells such as lymphocytes, hematopoietic stem cells and cancer cells, thereby contributing in part to drug resistance in leukaemia and other tumours [18,19] and in HIV [20].…”

Section: Abcb1 Expressionmentioning

confidence: 99%

Impact of Genetic Polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on Drug Disposition and Potential Clinical Implications: Update of the Literature

et al. 2015

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ATP-binding cassette transporter B1 (ABCB1; P-glycoprotein; multidrug resistance protein 1) is an adenosine triphosphate (ATP)-dependent efflux transporter located in the plasma membrane of many different cell types. Numerous structurally unrelated compounds, including drugs and environmental toxins, have been identified as substrates. ABCB1 limits the absorption of xenobiotics from the gut lumen, protects sensitive tissues (e.g. the brain, fetus and testes) from xenobiotics and is involved in biliary and renal secretion of its substrates. In recent years, a large number of polymorphisms of the ABCB1 [ATP-binding cassette, sub-family B (MDR/TAP), member 1] gene have been described. The variants 1236C>T (rs1128503, p.G412G), 2677G>T/A (rs2032582, p.A893S/T) and 3435C>T (rs1045642, p.I1145I) occur at high allele frequencies and create a common haplotype; therefore, they have been most widely studied. This review provides an overview of clinical studies published between 2002 and March 2015. In summary, the effect of ABCB1 variation on P-glycoprotein expression (messenger RNA and protein expression) and/or activity in various tissues (e.g. the liver, gut and heart) appears to be small. Although polymorphisms and haplotypes of ABCB1 have been associated with alterations in drug disposition and drug response, including adverse events with various ABCB1 substrates in different ethnic populations, the results have been majorly conflicting, with limited clinical relevance. Future research activities are warranted, considering a deep-sequencing approach, as well as well-designed clinical studies with appropriate sample sizes to elucidate the impact of rare ABCB1 variants and their potential consequences for effect sizes.

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Factors impacting the expression of membrane-bound proteins in lymphocytes from HIV-positive subjects

Cited by 18 publications

References 18 publications

ABCB1 gene expression in peripheral blood mononuclear cells in healthy Thai males and females

ABCB1 gene expression in peripheral blood mononuclear cells in healthy Thai males and females

Implication of P-Glycoprotein in Formation of Depression-Prone Personality: Association Study between the C3435T <b><i>MDR1</i></b> Gene Polymorphism and Interpersonal Sensitivity

Impact of Genetic Polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on Drug Disposition and Potential Clinical Implications: Update of the Literature

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