HLA-DRB Associated Susceptibility To Onychomycosis In Chinese Hans In Jiangsu And Anhui Province:a Preliminary Study

Onychomycosis is one of the most common lesion in clinical Dermatology, the causing pathogens including dermatophytes, yeasts (mainly Candida), and non-dermatophytes. Epidemiological studies have shown that the incidence of onychomycosis accounts for2%to11%of the general population,30%of the cutaneous fungal infections, and50%of all nail diseases. The treatment of onychomycosis has also been a thorny issue in the dermatology therapeutics. The course of treatment is long and the infection is easy to relapse and re-infect new species.Onychomycosis is more than discoloration, deformation, thickening, also affect the function of nail and the fine functions of the finger/toe tips. Onychomycosis is a long-term disease which also formed a potential source of fungal infection in the human body, the new fungal infections will occur in the rest of the body through the scratching of the infected nails, and can also be spread through direct contact to other individuals, the secondary bacterial infections can evoke severe diseases such as erysipelas, cellulitis, sepsis which can induce serious systemic disorders.With the development of the modern society, the improvement of people’s living environments and the increasingly extensive social interaction activities, the influence caused by onychomycosis on patients’physical and mental health is also growing. Many investigations revealed that onychomycosis impact on patients’daily life, physical and mental health, social activities in different extent; the degree of the impact is associated with the duration of the disease, the number of the infected nail and the effectiveness of the treatment. Therefore definitely clear the cause of onychomycosis is important for early prevention and treatment. In clinical practice, we discovered that a high prevalence of onychomycosis amongst family members. Although this phenomenon can be attributed to intrafamilial transmission, some investigations showed a low prevalence of onychomycosis among spouses that have married into infected families, together with a high incidence of onychomycosis amongst offspring. And the course of the disease, the clinical manifestations of the infected nail and the reaction to the medication are also different in different patients, suggests genetic susceptibility.There are several studies abroad have shown that HLA-DRB alleles associated with Trichophyton rubrum (T. rubrum) onychomycosis. Asz-Sigall D et al. and Garcia-Romero MT et al.’s investigations indicate that HLA-DR6(HLA-DRB1*06) and HLA-DR8(HLA-DRB1*08) may be antagonistic and susceptibility genes of T. rubrum onychomycosis in Mexicans Mestizo population, Zaitz C et al found that HLA-DR53(HLA-DRB4) may be a antagonistic gene to T. rubrum onychomycosis in Brazilian Ashkenazic Jews.HLA-DRB gene is one of the genes of HLA-Ⅱ class, HLA-Ⅱ class is located on human chromosome6near the centromere end of the HLA complex, including dozens of different gene loci, the classic class Ⅱ genes generally refers HLA-DR, HLA-DP and HLA-DQ, accounts about1.0Mkb. The DR sub-region including a DRA gene and nine DRB genes, DRB1, DRB3, DRB4, DRB5are functional genes, DRB2and DRB6-9are pseudogenes. DRB1gene express in all individuals, however, DRB3, DRB4, DRB5genes only express in different haplotypes, the expression of the sites mainly depends on the type of the expression of DRB1alleles. The HLA complex gene system is the most polymorphism district in the human gene system, up to July2006, the identified alleles of the HLA complex is about2641, and HLA-DRB1alleles as many as527. The polymorphism of the HLA-DRB alleles is reflected in the different allele distribution through the different racial, ethnic, geographical population distribution.For the foreign studies were limited to T. rubrum onychomycosis, which indicating that the HLA-DRB alleles associated with T. rubrum onychomycosis, but the results had significant differences in different regions and races, and still lack the research of other fungal infection, and there is no related research domestic. So we collect the onychomycosis patients without system disorders from the dermatology outpatient clinic, and use polymerase chain reaction-sequence specific primers (PCR-SSP) method to indentify the association of HLA-DRB alleles with onychomycosis in Chinese Hans in Jiangsu and Anhui province. Looking forward to find susceptible or antagonistic genes and provide new theories for the genetic diagnosis and treatment.1Analysis of127onychomycosis patients without systemic disorders in Nanjing General Hospital of Nanjing Military Command1.1ObjectiveTo investigate the general information, clinical types and etiologic agents of onychomycosis patients attending Nanjing General Hospital of Nanjing Military Command without systemic disorders.1.2MethodsA total of127suspected cases of onychomycosis in apparently healthy individuals attending the dermatology outpatient clinic at Nanjing General Hospital of Nanjing Military Command during November2011to May2012were enrolled. The general information of patients was collected. Nail samples were obtained and were subjected for direct microscopy and fungal culture.1.3Results1) General informationIn all the127cases, the male:female ratio was1:1.12. The mean age was38.94±15.51years (range:3～83years), and54(42.52%) of them work in the office.2) The infection of family members54cases (42.52%) of127patients have at least one first-degree relative suffering from onychomycosis. In the96cases of married ones, only15spouses (15.63%) suffering from onychomycosis. χ2=18.507, P=0.000<0.05, the difference was statistically significant.3) The general information of the infected nails.In60male patients, fingernail infection in4(6.67%) cases, toenail infection in35(58.33%) patients, both fingernail and toenail infection in21(35.00%) cases; In67female patients, fingernail infections in6(8.96%) cases, toenail infection in46(68.66%) cases, both fingernail and toenail infection in15(22.39%) cases. In total,117cases of toenail infection, the course range from one week to50years, an average of (8.33±0.91) years,46cases of fingernail infection, the course range from1month to50years, an average of (7.23±1.40) years.4) The clinical manifestationThe clinical manifestation of46infected fingernails are proximal subungual onychomycosis0case (0.00%), superficial white onychomycosis11cases (23.91%), total dystrophic onychomycosis9cases (19.57%), distal and lateral subungual onychomycosis26cases (56.52%). The clinical manifestation of117infected toenails are proximal subungual onychomycosis4cases (3.42%), superficial white onychomycosis14cases (11.97%), total dystrophic onychomycosis15cases (12.82%), distal and lateral subungual onychomycosis84cases (71.97%). In total, proximal subungual onychomycosis4cases (2.45%), superficial white onychomycosis25cases (15.34%), total dystrophic onychomycosis24cases (14.72%), distal and lateral subungual onychomycosis110cases (67.48%).5) The culture positive rate35cases (76.09%) of46fingernail specimens culture positive;85cases (72.65%) of117cases toenail specimens culture positive. Compare the positive rate,%2=0.201, P=0.654>0.05, No significant differences between two groups.6) culture results46fingernail samples and117toenail samples were collected, and120(73.62%) samples were positive for fungal elements by culture, dermatophytes were isolated in101(84.17%) samples, T. rubrum89(74.17%) was the most common isolate, mixed infections with dermatophytes were isolated in13(10.83%) samples, the yeasts isolated in5(4.17%) samples and the non-dermatophyte moulds only isolated in1(0.83%) sample.1.4Conclusions1) In all the127cases, the male:female ratio was1:1.12,54(42.52%) of them work in the office; isolated fingernail or toenail infection is common to be seen at the age of21-30, both infection on the fingernail and toenail is common to be seen at the age of41-50.2) Genetic susceptibility plays a significant role in the pathogenesis of onychomycosis in patients without systemic disorders.3) Distal and lateral subungual onychomycosis is the commonest clinical manifestation, proximal subungual onychomycosis is the rarest clinical manifestation,4) The culture positive rate was73.62%. There was no significant difference between the fingernail/toenail culture positive rate.5) This survey reveals that the etiologic agents of onychomycosis in apparently healthy individuals are mainly dermatophytes. Although the yeast and non-dermatophyte moulds infection is rare in this population, the rate of mixed infection with dermatophytes is significant. So in the clinical practice, the mycological examination is important for this population, especially in the refractory ones’, the broad-spectrum antifungal agents should be considerate first in necessary.2HLA-DRB associated susceptibility to onychomycosis in Chinese Hans in Jiangsu and Anhui Province:A preliminary study2.1ObjectiveThe aim of our study was to identify the associated of HLA-DRB alleles with onychomycosis in Chinese Hans in Jiangsu and Anhui province.2.2MethodsPolymerase chain reaction sequence-specific primer (PCR-SSP) method was used to analyze the type of HLA-DRB alleles in48patients with T. rubrum onychomycosis,14patients with T. mentagrophytes onychomycosis and48healthy controls. All statistical tests were carried out using SPSS13.0for windows. Confidence intervals (CIs) were given at95%confidence, and differences were considered significant at P<0.05.2.3Results1) General information48cases of T. rubrum onychomycosis,24male,24female, age rank17-78years, average age35.56±14.71years;14cases of T. mentagrophytes onychomycosis,10male,4female, age rank22～42years, average age32.29±14.00years. The health control group is sex and age marched with T. rubrum onychomycosis group, totally48cases,24male,24female, age rank17～76years, average age35.60±14.36years.2) Thirteen DRB1alleles were identified in the T. rubrum onychomycosis and the health controls, including:DRB1*01、*03、*04、*07、*08、*09、*10、*11、*12、*13、*14、*15、*16; ten DRB1alleles were identified in T. mentagrophytes onychomycosis, including:DRB1*01、*03、*04、*07、*09、*11、*12、*13、*14、*16, and DRB1*08、*10、*15alleles was not indentified。3) All the HLA-DRB1allele frequencies were similar between T. rubrum onychomycosis patients and controls, the HLA-DRB1frequencies observed in both groups showed no significant values (P>0.05).4) When compare between patients due to T. mentagrophytes and healthy controls. The HLA-DRB1*14allele was found in five (17.86%) cases and3(3.13%) controls, which was statistically significant (P=0.005<0.05) with an OR of6.739(95%CI:1.500-30.274); the HLA-DRB1*15allele was found in zero (0.00%) cases and16(16.67%) controls (P=0.021<0.05, OR0.833,95%CI:0.762-0.911)5) HLA-DRB3、DRB4、DRB5allele frequencies observed in T. rubrum onychomycosis patients and controls showed no significant values (P>0.05).6) HLA-DRB3、DRB4、DRB5allele frequencies observed in T. mentagrophytes onychomycosis patients and controls showed no significant values (P>0.05).2.4Conclusions1) HLA-DRB1alleles may not association with T. rubrum onychomycosis in Chinese Hans in Jiangsu and Anhui province.2) HLA-DRB1*14allele could be the susceptible allele of T. mentagrophytes onychomycosis, while HLA-DRB1*15could be the protective allele in Chinese Hans in Jiangsu and Anhui province;3) HLA-DRB3、DRB4、DRB5alleles may not association with T. rubrum onychomycosis in Chinese Hans in Jiangsu and Anhui province.4) HLA-DRB3、DRB4、DRB5alleles may not association with T. mentagrophytes onychomycosis in Chinese Hans in Jiangsu and Anhui province. 5) There may be different genetic backgrounds among onychomycosis with different fungi infection in Chinese Hans in Jiangsu and Anhui province.