Certain commonly occurring single-nucleotide polymorphisms in OATP-C, such as T521C (Val174Ala), are likely to be associated with altered pharmacokinetics of pravastatin. Large clinical studies are needed to confirm these observations.

Coordination polymers (CPs) have large degrees of freedom in framework compositions and in the structures and environment of the inner pores. This review focuses on the recent significant progress achieved by controlling these degrees of freedom. Two breakthroughs are reviewed for constructing sophisticated structures of CP frameworks, especially in dimensional crossover regions. The first is the synthesis of quasi one-dimensional halogen-bridged coordinative tubes by applying state-of-the-art techniques of coordination chemistry. The electronic state of the coordinative tube was studied by structural, spectroscopic and theoretical methods and found to be distinct from conventional one-dimensional systems. The second breakthrough is the achievement of a quasi-two-dimensional architecture by combining Langmuir-Blodgett and layer-by-layer methods. Two-dimensional LB CP films were prepared on liquid; the films were stacked layer by layer, and a crystalline quasi-two-dimensional structure was constructed. This review also covers the design of the environment of the inner pore, where hydrogen bond networks with various acidic sites were modified. By appropriate design of the hydrogen bond network, proton-conductive CPs are invented, which are summarized in this review. Types of proton donor sites are discussed and classified, and superprotonic conductive CPs were achieved in these investigations. These results will provide new strategies for constructing functional materials for smart devices.

Both VKORC1 and CYP2C9 polymorphisms contribute to inter-population difference in warfarin doses among the three populations, but their contribution to intra-population variability may differ within each population.

ABSTRACT:The aim of the present study was to assess the contribution of polymorphisms in the breast cancer resistance protein/ATP-binding cassette transporter G2 (BCRP/ABCG2) gene to the placental expression from a new perspective, allelic imbalance. Polymorphisms were screened by polymerase chain reaction (PCR)-singlestrand conformation polymorphism analysis followed by sequencing with DNA extracted from 100 placentas. To evaluate whether the C421A polymorphism acts as a cis-element in BCRP transcription, allelic imbalance was determined using informative lymphoblasts and 56 samples of placental cDNA. In most of the placental samples we tested, the difference in expression levels between the two alleles was small, and only two samples indicated a monoallelic expression (i.e., preferential expression of one allele). These results suggest that 1) the predominant allelic expression pattern of BCRP in placental samples is biallelic, and 2) the mutation C421A is not a genetic variant acting in cis, but is considered to influence the translation efficiency.Breast cancer resistance protein (BCRP), also called mitoxantroneresistant protein, is the second member of the G family of ATPbinding cassette transporters (ABCG2) (Allikmets et al., 1998;Doyle et al., 1998;Miyake et al., 1999;Doyle and Ross, 2003). The BCRP gene is located at 4q22 and encodes a 72-kDa membrane protein composed of 655 amino acids (Allikmets et al., 1998;Doyle et al., 1998;Allen et al., 1999;Bailey-Dell et al., 2001). In contrast to many other ABC transporters, BCRP has only one ATP-binding region and one transmembrane domain. Therefore, BCRP is referred to as a half-transporter, and its homodimerization may be necessary to transport substrates .In normal human tissues, BCRP is highly expressed in the placenta, colon, small intestine, and liver (Maliepaard et al., 2001). On the basis of its tissue distribution and findings in knockout mice, BCRP is speculated to have a major influence on the pharmacokinetic and pharmacodynamic profiles of certain xenobiotics and endogenous substrates. For example, inhibition of mouse Bcrp 1 by GF120918, a dual inhibitor for BCRP and P-glycoprotein, has been demonstrated to increase the bioavailability of topotecan when GF120918 was administered orally to mdr1a/1b(Ϫ/Ϫ) mice (Jonker et al., 2000). In a clinical study, coadministration of GF120918 was also associated with a marked increase in the bioavailability of and systemic exposure to topotecan (Kruijtzer et al., 2002).Recent clinical studies indicate that the large interindividual variability in drug response occurs as a result of molecular alterations to various proteins such as drug-metabolizing enzymes, drug targets and receptors, and drug transporters. Most studies on molecular alterations have focused on the impact of single-nucleotide polymorphisms (SNPs) on the expression and function of these proteins (Evans and Relling, 1999;Evans and Johnson, 2001). Several groups have reported naturally occurring SNPs in the BCRP gene. G34A and C421A occur at relative...