Drug Transporters

Blood and tissue concentrations of most drugs are influenced by interindividual variation in the structure and function of the metabolizing enzyme and transporter genes. Transporters are genes that control drug uptake, distribution, and elimination. The multidrug resistance gene (MDR1) encodes for a P-glycoprotein (PgP), which belongs to the large adenosine triphosphate (ATP)-binding cassette (ABC) protein. The MDR1 gene was originally discovered as the protein causing cross-resistance of tumors to many different cyto-toxic agents (16). Multiple substrates are transported by PgP, including the chemotherapeutics tamoxifen and mitoxantrone, the antibiotics cefotetan and cefazolin, the immunosuppressant cyclosporin A, the antiarrytmic drug quindine, the cardiac stimulants digoxin, and such opioid drugs as morphine, to name a few (17). Many cancers are known to overexpress the PgP protein, and this has been correlated with poor prognosis, particularly in patients with leukemia (18). Several SNPs have been reported in the MDR1 gene, some of which have been correlated with PgP protein expression, notably including the C/T polymorphism in exon 26 (19). In a recent study (20), antiviral response to nelfi-navir and efavirenez was shown to correlate with the allelic variant, 3435C/T, of the MDR1 gene. Patients who were homozygotes, carrying two copies of the 3435 T allele, demonstrated lower serum concentration, faster recovery in CD4 T cell count, and more rapid decrease in viral load, suggesting that the MDR1 3435C/T variant may be predictive of immune recovery after antiviral treatment in HIV patients (20). Approximately 50% of Caucasians are heterozygote (C/T) at the 3435 MDR1 polymorphic site, while a homozygote state (C/C) or (T/T), is seen in 25% of individuals, respectively. In contrast, the frequency of the CC genotype in African Americans is 67% to 83%, whereas the frequency of the TT allele is very low. Increased expression of PgP has also been correlated with variation in clinical response to glucocorticoids in patients with inflammatory bowel disease (21) and systemic lupus erythematosus (22). Collectively, these studies suggest that there are important variations in the MDR1 gene that regulate tumor resistance, immune function, and metabolism of multiple drugs.

Cure Your Yeast Infection For Good

Cure Your Yeast Infection For Good

The term vaginitis is one that is applied to any inflammation or infection of the vagina, and there are many different conditions that are categorized together under this ‘broad’ heading, including bacterial vaginosis, trichomoniasis and non-infectious vaginitis.

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