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Clinical and Molecular Evidence of ABCC11 Protein Expression in Axillary Apocrine Glands of Patients with Axillary Osmidrosis.

ABSTRACT: Accumulating evidence suggests that the risk of axillary osmidrosis is governed by a non-synonymous single nucleotide polymorphism (SNP) 538G>A in human ATP-binding cassette C11 (ABCC11) gene. However, little data are available for the expression of ABCC11 protein in human axillary apocrine glands that produce apocrine sweat-a source of odor from the armpits. To determine the effect of the non-synonymous SNP ABCC11 538G>A (G180R) on the ABCC11 in vivo, we generated transiently ABCC11-expressing transgenic mice with adenovirus vector, and examined the protein levels of each ABCC11 in the mice with immunoblotting using an anti-ABCC11 antibody we have generated in the present study. Furthermore, we examined the expression of ABCC11 protein in human axillary apocrine glands extracted from axillary osmidrosis patients carrying each ABCC11 genotype: 538GG, GA, and AA. Analyses of transiently ABCC11-expressing transgenic mice showed that ABCC11 538G>A diminishes the ABCC11 protein levels in vivo. Consistently, ABCC11 protein was detected in the human axillary apocrine glands of the 538GG homozygote or 538GA heterozygote, not in the 538AA homozygote. These findings would contribute to a better understanding of the molecular basis of axillary osmidrosis.

SUBMITTER: Toyoda Y

PROVIDER: S-EPMC5343951 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Clinical and Molecular Evidence of ABCC11 Protein Expression in Axillary Apocrine Glands of Patients with Axillary Osmidrosis.

Toyoda Yu Y Takada Tappei T Gomi Tsuneaki T Nakagawa Hiroshi H Ishikawa Toshihisa T Suzuki Hiroshi H

International journal of molecular sciences 20170215 2

Accumulating evidence suggests that the risk of axillary osmidrosis is governed by a non-synonymous single nucleotide polymorphism (SNP) 538G>A in human ATP-binding cassette C11 (ABCC11) gene. However, little data are available for the expression of ABCC11 protein in human axillary apocrine glands that produce apocrine sweat-a source of odor from the armpits. To determine the effect of the non-synonymous SNP ABCC11 538G>A (G180R) on the ABCC11 in vivo, we generated transient ...[more]

PMID: 28212277

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Project description:Two types of cerumen occur in humans: the wet type with brownish, sticky earwax, and the dry type with a lack of or reduced ceruminous secretion. The wet type is common in populations of European and African origin, while the dry type is frequently seen in Eastern Asian populations. An association between axillary odor and the wet-type earwax was first identified approximately 70 years ago. The data were based on a phenotypical analysis of the two phenotypes among the Japanese by a researcher or by self-declaration of the subjects examined, and were not obtained using definite diagnostic methods. Recently, we identified a single-nucleotide polymorphism (SNP; rs17822931) of the ABCC11 gene as the determinant of the earwax types. In the present study, to determine whether the SNP can serve as a diagnostic marker for axillary osmidrosis (AO), we examined genotypes at rs17822931 in 79 Japanese AO individuals. AO was defined here as a clinical condition of individuals with a deep anxiety regarding axillary odor and had undergone the removal of bilateral axillary apocrine glands.A comparison of the frequencies of genotypes at rs17822931 in the 79 AO individuals and in 161 Japanese from the general population showed that AO was strongly associated with the wet earwax genotype. A total of 78 (98.7%) of 79 AO patients had either the GG or GA genotype, while these genotypes were observed in 35.4% (57/161) of the subjects from the general population (p < 1.1 x 10(-24), by Fisher's exact test).The strong association between the wet-earwax associated ABCC11-genotypes (GG and GA) and AO identified in this study indicates that the genotypes are good markers for the diagnosis of AO. In addition, these results suggest that having the allele G is a prerequisite for the axillary odor expression. In other words, the ABCC11 protein may play a role in the excretory function of the axillary apocrine gland. Together, these results suggest that when an AO individual visiting a hospital is diagnosed with dry-type earwax by ABCC11-genotyping, surgical removal of their axillary glands may not be indicated.

Project description:Axillary osmidrosis (AO) is a common disease that causes patients to develop malodor and occurs worldwide. There is a lack of uniform standards to evaluate the severity of the odor and identify a sensitive and convenient method to determine the therapeutic effect of AO treatments in a clinical setting. In the present study, the association between pH value and disease severity was investigated and the potential pathogenic bacteria and probiotic pathogens of AO were further examined. A total of 32 patients with bilateral AO and 32 normal healthy controls were recruited for the present study. The odor was investigated using the traditional method (TM) and our groups newly developed Lu swab method (LSM) and according to the results, the cases were assigned a score on a 4-point scale. The patients' scores and pH value were recorded. The microbiological compositions of the affected sites were determined using 16S rDNA sequencing. The mean LSM score was higher compared with the mean TM score (P<0.05). Furthermore, the mean axillary pH value was higher in patients with AO compared with that in healthy subjects (P<0.0001), and the mean pH value of patients with high disease severity was higher compared with that in patients with moderate disease severity (P<0.001). In the microecological flora, the proportion of Staphylococcus species on patients with AO was significantly lower compared with that on normal controls (P<0.0001), while the proportion of Corynebacterium and Anaerococcus was significantly higher compared with that on normal controls (P<0.01 and P<0.001, respectively). In conclusion, LSM provided a higher sensitivity for evaluating odor severity than the TM and may be suitable for use in a clinical setting. The pH value was positively associated with AO severity. Staphylococcus may be an appropriate probiotic for the treatment of AO, while Corynebacterium and Anaerococcus may be causative pathogens of AO. The present study was registered in the Chinese Clinical Trial Registry (registration no. ChiCTR2000037275).

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Dataset Information

Clinical and Molecular Evidence of ABCC11 Protein Expression in Axillary Apocrine Glands of Patients with Axillary Osmidrosis.

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Clinical and Molecular Evidence of ABCC11 Protein Expression in Axillary Apocrine Glands of Patients with Axillary Osmidrosis.

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