Study On The Pathogenesis Of Axillary Osmidrosis By Metabonomics And The Clinical Characeteristics Of Axillary Osmidrosis

Background Axillary Osmidrosis(AO)is a clinical disease characterized by unpleasant odor.Although axillary osmidrosis does not affect physical health,it will affect the mental health.Patients often have a heavy psychological burden and become less confident or low self-esteem,affecting daily life and social life,and even depression in severe cases.At present,there are many clinical methods to treat axillary osmidrosis.However,these methods have more or less defects.At present,the specific pathogenesis of axillary osmidrosis is not clear.It is known that there are many influencing factors of axillary osmidrosis,including gene,gender,age,diet,emotion,axillary microorganism,family history and treatment history.Previous studies of our research group have proved that the genetic variation ABCC11 rs17822931 is associated with the susceptibility of axillary osmidrosis.Different genotypes have certain effects on the growth,proliferation and metabolism of apocrine sweat glands,but the specific mechanism of how ABCC11 gene causes axillary osmidrosis is not clear.At the same time,ABCC11 gene polymorphism can’t well explain the characteristics of puberty in patients with axillary osmidrosis.Previous studies have shown that ABCC11,AR and APOD,which is expressed in apocrine sweat gland tissue of patients with axillary osmidrosis,may be involved in the occurrence of axillary osmidrosis.However,the possible role of them in the occurrence of axillary osmidrosis has not been reported.It is not clear whether APOD and AR gene polymorphisms are also related to the susceptibility to axillary osmidrosis like ABCC11 gene polymorphism.In order to study the pathogenesis of axillary osmidrosis,we detected the gene polymorphism and the protein expression level in apocrine sweat gland tissue of patients with axillary osmidrosis.We discussed the pathogenesis of axillary osmidrosis from metabonomics for the first time.We analyzed the possible metabolic pathways involved in axillary osmidrosis by combining multi omics research,and further clarified the role of ABCC11,AR and APOD in the pathogenesis of axillary osmidrosis.It is expected to provide a new direction for the treatment of axillary osmidrosis and the research and development of related drugs.At the same time,this study also collected and compared the clinical data of axillary osmidrosis in Han population in two different eating habits areas,and summarized the incidence characteristics of axillary osmidrosis,hoping to provide a scientific basis for the clinical diagnosis of axillary osmidrosis.Objective1.To compare the expression level of ABCC11,APOD,sex hormone receptor(AR and ER-β)related proteins in axillary apocrine sweat gland between patients with axillary osmidrosis and controls,and further explore the pathogenesis of axillary osmidrosis.2.The relationship between APOD and AR gene polymorphisms and the susceptibility of axillary osmidrosis.3.To measure the differentially expressed small molecule metabolites between patients with axillary osmidrosis and normal controls,and analyze the possible metabolic pathways in patients with axillary osmidrosis.With the help of metabolomic information analysis platform,so as to provide a new idea for the treatment of axillary osmidrosis.4.To analyze the clinical characteristics of axillary osmidrosis and the related factors that may affect the degree of axillary osmidrosis,so as to provide scientific basis for the clinical diagnosis of axillary osmidrosis;Methods1.The axillary skin samples of axillary osmidrosis group and normal group were collected.The ABCC11,APOD,sex hormone receptor(AR and ER-β)related proteins in apocrine sweat glands were detected by immunohistochemical method,and the differences between the two groups were compared to clarify their expression in axillary apocrine sweat glands.2.In order to explore the relationship between AR and APOD gene polymorphisms and susceptibility of axillary osmidrosis,we selected 11 candidate non synonymous single nucleotide polymorphisms(SNPs)from the published papers on the gene loci of AR and APOD non synonymous single nucleotide polymorphisms and the haploview.The Sequenom Mass ARRAY i PLEX platform(sequenom,Inc.,San Diego,CA)was used for genotyping of candidate SNPs.The significant difference of AR and APOD genotype frequency between axillary osmidrosis group and normal group was detected by i PLEX Gold technology.3.Twelve pairs of serum from axillary osmidrosis group and normal group were collected,and non-targeted metabonomics analysis was carried out with the help of gas chromatography-mass spectrometry analysis platform to screen potential differential metabolic markers in patients with axillary osmidrosis.Metabo Analyst 4.0 platform was used to analyze the metabolic pathway of the potential endogenous differential metabolites obtained above.Integrated molecular pathway level analysis(IMPa LA)found that the overexpression of ABCC11,APOD and AR genes and endogenous differential small molecule metabolites,and screened the signal pathways that may be involved in the pathogenesis of axillary osmidrosis.4.The clinical information of 991 patients with axillary osmidrosis was collected,including the age,gender,family history,earwax traits,degree of axillary osmidrosis and body mass index.The clinical characteristics of patients with axillary osmidrosis and the relationship between the degree of axillary osmidrosis and gender,age and body mass index were analyzed to explore the possible influencing factors in the pathogenesis of axillary osmidrosis.Results1.The expression of ABCC11,APOD and AR proteins in apocrine sweat glands of the axillary osmidrosis group is increased,and suggested that ABCC11,APOD and AR proteins may be involved in the pathogenesis of axillary osmidrosis(P < 0.05).2.There were significant differences in genotype frequencies of AR rs 72627670(P = 0.026 < 0.05)and APOD rs 2056469(P = 0.039 < 0.05)between patients with axillary osmidrosis and controls.3.Non-targeted metabolomics analysis found that there are 15 kinds of small molecule metabolites with the significant difference in patients with axillary osmidrosis,which may involve amino acid metabolism(arginine and proline metabolism,lysine degradation,glycine,serine and threonine metabolism),glucose metabolism(especially galactose metabolism;amino sugar and nucleotide sugar metabolism)and phospholipid metabolism(glycerol phospholipid metabolism)and aminoacyl transfer ribonucleic acid biosynthesis metabolism.Bioinformatics analysis of overexpressed small molecule metabolites and related gene proteins(ABCC11,AOPD and AR)revealed that the main metabolic pathways involved in patients with axillary osmidrosis were androgen and estrogen biosynthesis and metabolism,ABC protein transport,ABC Family protein transport,etc(P < 0.05).4.A total of 991 patients were collected,and the average age is 23.57 ± 5.35 years.There was 894 patients with family history(90.21%)and 956 patients with oily earwax(96.47%).The body mass index of patients with mild,moderate and severe axillary osmidrosis were 20.66 ± 2.42,22.30 ± 3.58 and 22.33 ± 2.98.The degree of axillary osmidrosis may be positively correlated with body mass index(P < 0.05).Conclusions1.The expression of ABCC11,APOD and AR proteins in apocrine sweat glands was increased in AO patients,suggesting that ABCC11,APOD and AR proteins may be involved in the pathogenesis of axillary osmidrosis.2.The gene polymorphisms of AR rs72627670 and APOD rs2056469 were associated with the susceptibility of axillary osmidrosis.3.There are 15 kinds of small molecule metabolites with the most significant difference in the serum of patients with axillary osmidrosis compared with control.The main differential metabolism included amino acid metabolism,glucose metabolism,phospholipid metabolism and aminoacyl transfer RNA biosynthesis.The pathogenesis of axillary osmidrosis is mainly involves biosynthesis and metabolic pathway of androgen and estrogen,but the specific mechanism needs further studied.The above findings may provide a new research direction for the diagnosis and treatment of axillary osmidrosis.4.Axillary osmidrosis is affected by heredity,gene and metabolism.Family history of axillary osmidrosis and history of wet earwax can be used as one of the criteria to assist in the early diagnosis of axillary osmidrosis.The severity of axillary osmidrosis is closely related to age and body mass index.We found that the main group of patients with axillary osmidrosis was 17-29 years old,and the proportion of patients over 30 years old decreased.At the same time,we found that after the age of 30,the degree of axillary odor will gradually decrease.The above findings may provide a new basis for the in-depth study of axillary osmidrosis.