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Pharmacogenetics of human ABC transporter ABCC11: new insights into apocrine gland growth and metabolite secretion.

Ishikawa T, Toyoda Y, Yoshiura K, Niikawa N - Front Genet (2013)

Bottom Line: Cell secretion is an important physiological process that ensures smooth metabolic activities and tissue repair as well as growth and immunological functions in the body.The wild-type (Gly180) of ABCC11 is associated with wet-type earwax, axillary osmidrosis, and colostrum secretion from the mammary gland as well as the potential risk of mastopathy.Furthermore, the SNP (538G > A) in the ABCC11 gene is suggested to be a clinical biomarker for the prediction of chemotherapeutic efficacy.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology Yokohama, Japan ; Omics Science Center, RIKEN Yokohama Institute Yokohama, Japan.

ABSTRACT
Cell secretion is an important physiological process that ensures smooth metabolic activities and tissue repair as well as growth and immunological functions in the body. Apocrine secretion occurs when the secretory process is accomplished with a partial loss of cell cytoplasm. The secretory materials are contained within secretory vesicles and are released during secretion as cytoplasmic fragments into the glandular lumen or interstitial space. The recent finding that the non-synonymous single nucleotide polymorphisms (SNP) 538G > A (rs17822931; Gly180Arg) in the ABCC11 gene determines the type of earwax in humans has shed light on the novel function of this ABC (ATP-binding cassette) transporter in apocrine glands. The wild-type (Gly180) of ABCC11 is associated with wet-type earwax, axillary osmidrosis, and colostrum secretion from the mammary gland as well as the potential risk of mastopathy. Furthermore, the SNP (538G > A) in the ABCC11 gene is suggested to be a clinical biomarker for the prediction of chemotherapeutic efficacy. The aim of this review article is to provide an overview on the discovery and characterization of genetic polymorphisms in the human ABCC11 gene and to explain the impact of ABCC11 538G > A on the apocrine phenotype as well as the anthropological aspect of this SNP in the ABCC11 gene and patients' response to nucleoside-based chemotherapy.

No MeSH data available.


Related in: MedlinePlus

Detection of SNP 538G A in ABCC11 gene. (A) Strategy and primers for the SmartAmp-based detection of SNP 538G > A residing in exon 4 of the ABCC11 gene on chromosome 16q12 (upper panel) and the sequences of ABCC11 allele–specific primers needed for the SNP detection (lower panel). Arrows indicated the sequence difference between the WT and SNP alleles. (B) Time-courses of the SNP-detection reaction with ABCC11 allele-specific primers. Data are from Toyoda et al. (2009).
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FA2: Detection of SNP 538G A in ABCC11 gene. (A) Strategy and primers for the SmartAmp-based detection of SNP 538G > A residing in exon 4 of the ABCC11 gene on chromosome 16q12 (upper panel) and the sequences of ABCC11 allele–specific primers needed for the SNP detection (lower panel). Arrows indicated the sequence difference between the WT and SNP alleles. (B) Time-courses of the SNP-detection reaction with ABCC11 allele-specific primers. Data are from Toyoda et al. (2009).

Mentions: The rapid growth of personalized medicine is being supported by emerging new technologies together with accumulating knowledge of pharmacogenomics. We tried to create a clinical method, the SmartAmp, to genotype the SNP 538G > A in the human ABCC11 gene. The SmartAmp-based method enables us to detect genetic polymorphisms or mutations in about 30 min under isothermal conditions without requiring DNA isolation and PCR processes for sample preparation (Ishikawa and Hayashizaki, 2012). Figure A2A schematically illustrates the strategy of SNP detection by this clinical method. To determine the SNP 538G > A (Gly180Arg) in the ABCC11 gene, we prepared one set of primers designated TP, FP, BP, OP, and CP (Figure A2A). The TPS discriminate the polymorphism 538G or 538A in the ABCC11 gene, and the CPS inhibit the background amplification from mismatch sequence pairs (Toyoda et al., 2009; Ishikawa and Hayashizaki, 2012). These primers selectively recognized the SNP 538G > A of the ABCC11 gene to discriminate homozygous 538G/G, heterozygous 538G/A, and homozygous 538A/A (Figure A2A). Thus, this genotyping method would provide a practical tool to support clinical diagnosis (Ishikawa and Hayashizaki, 2012).


Pharmacogenetics of human ABC transporter ABCC11: new insights into apocrine gland growth and metabolite secretion.

Ishikawa T, Toyoda Y, Yoshiura K, Niikawa N - Front Genet (2013)

Detection of SNP 538G A in ABCC11 gene. (A) Strategy and primers for the SmartAmp-based detection of SNP 538G > A residing in exon 4 of the ABCC11 gene on chromosome 16q12 (upper panel) and the sequences of ABCC11 allele–specific primers needed for the SNP detection (lower panel). Arrows indicated the sequence difference between the WT and SNP alleles. (B) Time-courses of the SNP-detection reaction with ABCC11 allele-specific primers. Data are from Toyoda et al. (2009).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539816&req=5

FA2: Detection of SNP 538G A in ABCC11 gene. (A) Strategy and primers for the SmartAmp-based detection of SNP 538G > A residing in exon 4 of the ABCC11 gene on chromosome 16q12 (upper panel) and the sequences of ABCC11 allele–specific primers needed for the SNP detection (lower panel). Arrows indicated the sequence difference between the WT and SNP alleles. (B) Time-courses of the SNP-detection reaction with ABCC11 allele-specific primers. Data are from Toyoda et al. (2009).
Mentions: The rapid growth of personalized medicine is being supported by emerging new technologies together with accumulating knowledge of pharmacogenomics. We tried to create a clinical method, the SmartAmp, to genotype the SNP 538G > A in the human ABCC11 gene. The SmartAmp-based method enables us to detect genetic polymorphisms or mutations in about 30 min under isothermal conditions without requiring DNA isolation and PCR processes for sample preparation (Ishikawa and Hayashizaki, 2012). Figure A2A schematically illustrates the strategy of SNP detection by this clinical method. To determine the SNP 538G > A (Gly180Arg) in the ABCC11 gene, we prepared one set of primers designated TP, FP, BP, OP, and CP (Figure A2A). The TPS discriminate the polymorphism 538G or 538A in the ABCC11 gene, and the CPS inhibit the background amplification from mismatch sequence pairs (Toyoda et al., 2009; Ishikawa and Hayashizaki, 2012). These primers selectively recognized the SNP 538G > A of the ABCC11 gene to discriminate homozygous 538G/G, heterozygous 538G/A, and homozygous 538A/A (Figure A2A). Thus, this genotyping method would provide a practical tool to support clinical diagnosis (Ishikawa and Hayashizaki, 2012).

Bottom Line: Cell secretion is an important physiological process that ensures smooth metabolic activities and tissue repair as well as growth and immunological functions in the body.The wild-type (Gly180) of ABCC11 is associated with wet-type earwax, axillary osmidrosis, and colostrum secretion from the mammary gland as well as the potential risk of mastopathy.Furthermore, the SNP (538G > A) in the ABCC11 gene is suggested to be a clinical biomarker for the prediction of chemotherapeutic efficacy.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology Yokohama, Japan ; Omics Science Center, RIKEN Yokohama Institute Yokohama, Japan.

ABSTRACT
Cell secretion is an important physiological process that ensures smooth metabolic activities and tissue repair as well as growth and immunological functions in the body. Apocrine secretion occurs when the secretory process is accomplished with a partial loss of cell cytoplasm. The secretory materials are contained within secretory vesicles and are released during secretion as cytoplasmic fragments into the glandular lumen or interstitial space. The recent finding that the non-synonymous single nucleotide polymorphisms (SNP) 538G > A (rs17822931; Gly180Arg) in the ABCC11 gene determines the type of earwax in humans has shed light on the novel function of this ABC (ATP-binding cassette) transporter in apocrine glands. The wild-type (Gly180) of ABCC11 is associated with wet-type earwax, axillary osmidrosis, and colostrum secretion from the mammary gland as well as the potential risk of mastopathy. Furthermore, the SNP (538G > A) in the ABCC11 gene is suggested to be a clinical biomarker for the prediction of chemotherapeutic efficacy. The aim of this review article is to provide an overview on the discovery and characterization of genetic polymorphisms in the human ABCC11 gene and to explain the impact of ABCC11 538G > A on the apocrine phenotype as well as the anthropological aspect of this SNP in the ABCC11 gene and patients' response to nucleoside-based chemotherapy.

No MeSH data available.


Related in: MedlinePlus