A missense variant of the ABCC11 gene is associated with Axillary Osmidrosis susceptibility and clinical phenotypes in the Chinese Han Population

Ren, Yunqing; Liu, Wenting; Chen, Jisu; Wang, Jianyou; Wang, Ke; Zhou, Jiong; Cai, Sheng; Zheng, Min; Liu, Jing; Liu, Lunfei; Xue, Dan

doi:10.1038/srep46335

Cited by 9 publications

(8 citation statements)

References 20 publications

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“…The production of malodor on the underarm skin is primarily attributed to the action of the resident microbiota on odorless natural secretions from the apocrine gland ( 24 ). Corynebacterium is one of the dominant bacterial groups in the armpit microbiota, which has an important role in malodor generation ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Microecological investigation and comparison of two clinical methods to evaluate axillary osmidrosis

Ding

Gao

et al. 2020

Mol Med Rep

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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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Section: Discussionmentioning

confidence: 99%

Microecological investigation and comparison of two clinical methods to evaluate axillary osmidrosis

Ding

Gao

et al. 2020

Mol Med Rep

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“…ABCC11 encodes ATP binding cassette subfamily C member 11, which is a member of the multi-drug resistance protein (MRP) sub-family of the ATP-binding cassette gene family. The missense SNP has previously been associated with dry versus wet earwax types 118 and axillary ozmidrosis (body odor) 119 – 121 . The current study is the first report that shows that this SNP is also associated with hyperhidrosis.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study in Japanese females identifies fifteen novel skin-related trait associations

Endo

Johnson

Morino³

et al. 2018

Sci Rep

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Skin trait variation impacts quality-of-life, especially for females from the viewpoint of beauty. To investigate genetic variation related to these traits, we conducted a GWAS of various skin phenotypes in 11,311 Japanese women and identified associations for age-spots, freckles, double eyelids, straight/curly hair, eyebrow thickness, hairiness, and sweating. In silico annotation with RoadMap Epigenomics epigenetic state maps and colocalization analysis of GWAS and GTEx Project eQTL signals provided information about tissue specificity, candidate causal variants, and functional target genes. Novel signals for skin-spot traits neighboured AKAP1/MSI2 (rs17833789; P = 2.2 × 10−9), BNC2 (rs10810635; P = 2.1 × 10−22), HSPA12A (rs12259842; P = 7.1 × 10−11), PPARGC1B (rs251468; P = 1.3 × 10−21), and RAB11FIP2 (rs10444039; P = 5.6 × 10−21). HSPA12A SNPs were the only protein-coding gene eQTLs identified across skin-spot loci. Double edged eyelid analysis identified that a signal around EMX2 (rs12570134; P = 8.2 × 10−15) was also associated with expression of EMX2 and the antisense-RNA gene EMX2OS in brain putamen basal ganglia tissue. A known hair morphology signal in EDAR was associated with both eyebrow thickness (rs3827760; P = 1.7 × 10−9) and straight/curly hair (rs260643; P = 1.6 × 10−103). Excessive hairiness signals’ top SNPs were also eQTLs for TBX15 (rs984225; P = 1.6 × 10−8), BCL2 (rs7226979; P = 7.3 × 10−11), and GCC2 and LIMS1 (rs6542772; P = 2.2 × 10−9). For excessive sweating, top variants in two signals in chr2:28.82-29.05 Mb (rs56089836; P = 1.7 × 10−11) were eQTLs for either PPP1CB or PLB1, while a top chr16:48.26–48.45 Mb locus SNP was a known ABCC11 missense variant (rs6500380; P = 6.8 × 10−10). In total, we identified twelve loci containing sixteen association signals, of which fifteen were novel. These findings will help dermatologic researchers better understand the genetic underpinnings of skin-related phenotypic variation in human populations.

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“…categorized by ClinVar as benign or likely benign (Figure 2C, Supplemental Table 1A). These candidates include a substitution in ATP-binding cassette transporter sub-family C member 11 (G180R, rs17822931) that has high allele frequencies within East Asian populations (75%) and is significantly correlated with Axillary Osmidrosis in Chinese Han populations (30) as well as increased risk for breast cancer in Japanese women (31). Further analyses of these 23 putatively deleterious pAIMs revealed they exhibit higher allele frequencies in East Asian versus European and African populations (Figure 2D).…”

Section: Resultsmentioning

confidence: 99%

Peptide Ancestry Informative Markers in Uterine Neoplasms from Women of European, African and Asian Ancestry

Bateman

Tarney

Abulez

et al. 2020

Preprint

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Deep proteogenomic analyses of diverse populations will improve our understanding of molecular drivers of disease, such as those underlying uterine neoplasms which exhibit marked racial disparities. The characterization of ancestry-linked peptide variants in disease-relevant patient tissues represents a foundational step towards investigating relationships linking patient ancestry with the proteome, genome and disease pathogenesis. We selected 1,037 nonsynonymous single nucleotide polymorphisms (nsSNPs) encoding missense amino acid substitutions occurring within putative tryptic peptides exhibiting high allele frequencies (≥ 50%) in European, African, and East Asian populations, termed peptide ancestry informative markers (pAIMs) and investigated these in cell line models and tissues of uterine neoplasms collected from women representing diverse ancestries. We quantified 62 pAIMs in total across >100 patient-derived samples by multiplexed, quantitative proteomic analyses. Our analyses of endometrial cancer cell lines established from European (n=7), African (n=3), and East Asian (n=3) women resulted in the quantitation of 43 pAIMs that significantly correlated with population-level allele frequencies consistent with global ancestry estimates defined by genotype analyses. We next investigated uterine leiomyoma (ULM) tissues from self-described African-American (n=31) and European-American (n=35) women and quantified 33 pAIMs that correlated with patient race. We validated 10 of these in an independent cohort of ULM tissues collected from women determined to be of European (n=16) and African (n=11) ancestry by genotype analyses. This validated subset was predominated by candidates of undetermined clinical significance (ClinVar) and included a substitution in GC vitamin D-binding protein, i.e. (D451E, rs7041), that exhibits a higher allele frequency in European (58%) versus African (7.3%) populations and correlates with altered GC protein and vitamin D levels. Comparison of cell line and tissue analyses revealed co-quantitation of pAIMs encoded within Protein-L-isoaspartate(D-aspartate) O-methyltransferase (V178I, >80% AF in African and East Asians), Serine/threonine-protein phosphatase CPPED1 (A19D, >75% AF in Africans) and AH receptor-interacting protein (Q228K, >99% AF in European and East Asians). We further assessed the performance of pAIMs to determine patient ancestry in silico relative to standard genotype estimates by random sampling analyses and find that as few as 20 population-specific pAIMs can determine ancestry proportions similarly to >260K SNPs (R2=0.9905). These efforts have quantified and validated pAIMs in diverse uterine neoplasms that represent a foundational set of ancestry-linked variant peptides observable by multiplexed proteomics and provides proof of concept that estimates of European, African and East Asian ancestry can be determined from routine proteomic analysis of disease-relevant patient cell lines and tissues. This work will support ongoing efforts focused on linking the proteome and genome with patient ancestry to better understand relationships with disease mechanisms driving racial disparities in the pathogenesis of uterine neoplasms.

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A missense variant of the ABCC11 gene is associated with Axillary Osmidrosis susceptibility and clinical phenotypes in the Chinese Han Population

Cited by 9 publications

References 20 publications

Microecological investigation and comparison of two clinical methods to evaluate axillary osmidrosis

Microecological investigation and comparison of two clinical methods to evaluate axillary osmidrosis

Genome-wide association study in Japanese females identifies fifteen novel skin-related trait associations

Peptide Ancestry Informative Markers in Uterine Neoplasms from Women of European, African and Asian Ancestry

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