Development of Transmission Ambient Pressure Laser Desorption Ionization/Postphotoionization Mass Spectrometry Imaging.

Laser-based high-resolution mass spectrometry imaging at ambient conditions has promising applications in life science. However, the ion yield during laser desorption/ablation is poor. Here, transmission atmospheric pressure laser desorption ionization combined with a compact postphotoionization (t-AP-LDI/PI) assembly with a krypton discharge lamp was developed for the untargeted imaging of various biomolecules. The spatial distributions of numerous lipid classes, fatty acids, neurotransmitters, and amino acids in the subregions of mouse cerebellum tissue were obtained. Compared with single laser ablation, the sensitivities for most analytes were increased by 1 to 3 orders of magnitude by dopant-assisted postphotoionization. After careful optimization, a spatial resolution of 4 µm could be achieved for the metabolites in mouse hippocampus tissue. Finally, the melanoma tissue slices were analyzed using t-AP-LDI/PI MSI, which revealed the metabolic heterogeneity of the melanoma microenvironment and exhibited the phenomenon of abnormal proliferation and invasion trends in tumor cells.

Licochalcone A restrains microphthalmia-associated transcription factor expression and growth by activating autophagy in melanoma cells via miR-142-3p/Rheb/mTOR pathway.

Licochalcone A (LCA) was found to possess anticancer effects. This study aimed to investigate the anticancer effects and mechanisms of LCA in melanoma. A375 and B16 melanoma cells were stimulated with LCA, MTT assay was used to assess cell proliferation. Expression of miR-142-3p, microphthalmia-associated transcription factor (MITF, which regulates melanin production) and autophagy-related genes was determined by Real-time PCR or western blot. The apoptosis was analyzed by flow cytometry and caspase-3 activity. The roles of miR-142-3p and Ras homolog enriched in brain (Rheb) in LCA-affected cells were investigated by gain- and loss-of functions. LCA inhibited proliferation and MITF expression, but increased apoptosis and autophagy of melanoma cells. Moreover, LCA elevated miR-142-3p expression, but decreased its target gene Rheb expression. The effects of LCA on melanoma cells were abrogated by miR-142-3p inhibitor or Rheb overexpression. LCA suppressed mTOR signaling activation via Rheb. Additionally, rapamycin (a mTOR antagonist) notably attenuated the effects of Rheb on the autophagy, proliferation, apoptosis, and MITF expression in LCA-treated melanoma cells. In conclusion, LCA restrained MITF expression and growth by activating autophagy in melanoma cells via miR-142-3p/Rheb/mTOR pathway. This study suggested that LCA might be a potential therapeutic candidate for prevention and treatment of melanoma.

Imaging of Polar and Nonpolar Species Using Compact Desorption Electrospray Ionization/Postphotoionization Mass Spectrometry.

Desorption electrospray ionization (DESI) mass spectrometry imaging (MSI) can simultaneously record the 2D distribution of polar biomolecules in tissue slices at ambient conditions. However, sensitivity of DESI-MSI for nonpolar compounds is restricted by low ionization efficiency and strong ion suppression. In this study, a compact postphotoionization assembly combined with DESI (DESI/PI) was developed for imaging polar and nonpolar molecules in tissue sections by switching off/on a portable krypton lamp. Compared with DESI, higher signal intensities of nonpolar compounds could be detected with DESI/PI. To further increase the ionization efficiency and transport of charged ions of DESI/PI, the desorption solvent composition and gas flow in the ionization tube were optimized. In mouse brain tissue, more than 2 orders of magnitude higher signal intensities for certain neutral biomolecules like creatine, cholesterol, and GalCer lipids were obtained by DESI/PI in the positive ion mode, compared with that of DESI. In the negative ion mode, ion yields of DESI/PI for glutamine and some lipids (HexCer, PE, and PE-O) were also increased by several-fold. Moreover, nonpolar constituents in plant tissue, such as catechins in leaf shoots of tea, could also be visualized by DESI/PI. Our results indicate that DESI/PI can expand the application field of DESI to nonpolar molecules, which is important for comprehensive imaging of biomolecules in biological tissues with moderate spatial resolution at ambient conditions.

Association analyses identifying two common susceptibility loci shared by psoriasis and systemic lupus erythematosus in the Chinese Han population.

BACKGROUND: Genome-wide association studies (GWASs) have revealed a large number of genetic risk loci for many autoimmune diseases. One clear finding emerging from the published genetic studies of autoimmunity is that different autoimmune diseases, such as psoriasis and systemic lupus erythematosus (SLE), share susceptibility loci. Our study explores additional susceptibility loci shared by psoriasis and SLE in the Chinese Han population. METHODS: In total, 20 single nucleotide polymorphisms (SNPs) in 17 previously reported psoriasis susceptibility loci and 34 SNPs from 24 previously reported SLE susceptibility loci were investigated in our initial psoriasis and SLE GWAS dataset. Among these SNPs, we selected two SNPs (rs8016947 and rs4649203) with association values of p<5×10(-2) for both diseases in the GWAS data for further investigation in psoriasis (7260 cases and 9842 controls) and SLE (2207 cases and 9842 controls) using a Sequenom MassARRAY system. RESULTS: We found that these two SNPs (rs8016947 and rs4649203) in two loci (NFKBIA and IL28RA) were associated with psoriasis and SLE with genome-wide significance (Pcombined<5×10(-8) in psoriasis and Pcombined<5×10(-8) in SLE): rs8016947 at NFKBIA (Pcombined-psoriasis=3.90×10(-10), Pcombined-SLE=1.08×10(-13)) and rs4649203 at IL28RA (Pcombined-psoriasis=3.91×10(-12), Pcombined-SLE=9.90×10(-9)). CONCLUSIONS: These results showed that two common susceptibility loci (NFKBIA and IL28RA) are shared by psoriasis and SLE in the Chinese Han population.

Polymorphisms at 16p13 are associated with systemic lupus erythematosus in the Chinese population.

BACKGROUND: Chromosomal region 16p13 has been reported to harbour variants associated with several autoimmune diseases, including type I diabetes, rheumatoid arthritis and multiple sclerosis. OBJECTIVE: To test whether variants in the 16p13 region are also associated with systemic lupus erythematosus (SLE) by performing a candidate locus study in the Chinese Han population. METHODS: Tag single nucleotide polymorphisms (SNPs) encompassing 50 kb upstream and downstream of the 250 kb linkage disequilibrium block, previously implicated in several autoimmune diseases, were analysed in 1047 patients with SLE and 1205 controls. The SNP showing the strongest association with SLE was then replicated in an independent cohort of 1643 cases and 5930 controls. RESULTS AND CONCLUSIONS: The association between SNP rs12599402 and SLE reached the genome-wide significance level (p<5 × 10⁻8). The SNP was likely to tag the same functional variant as previously reported in European populations. The results suggested that the chromosomal region at 16p13 contains common susceptibility genes for different immune-mediated disorders.

Confirmation of C4 gene copy number variation and the association with systemic lupus erythematosus in Chinese Han population.

The distribution of complement component 4 (C4) gene copy number (GCN) has been validated in European populations. Meanwhile, C4 gene has been identified as a susceptibility gene for systemic lupus erythematosus (SLE). However, the association and the possible phenotype significance remain to be determined intensely in the Chinese population. This study was designed to validate the distribution of C4 GCNs in Chinese Han and the correlation between C4 GCNs and SLE using quantitative real-time polymerase chain reaction in 924 SLE patients and 1,007 controls. The results presented distribution of C4 GCNs in healthy populations and also showed that lower C4 GCN was a risk factor for SLE and higher C4 GCN was a protective factor against the disease susceptibility, which was similar to the report in the Caucasian population. Furthermore, we found the association between C4A GCN and disease subphenotypes of arthritis with SLE. We conclude that the association of C4 GCN with SLE was replicated in Chinese Han population, which highlighted the importance of C4 in SLE pathogenesis of diverse populations.

Exercise-Diet Therapy Combined with Insulin Aspart Injection for the Treatment of Gestational Diabetes Mellitus: A Study on Clinical Effect and Its Impact.

Objective: To explore the clinical effect and impact of exercise-diet therapy combined with Insulin Aspart Injection on gestational diabetes mellitus (GDM). Methods: The objects of study were patients with pregestational diabetes mellitus (PGDM) and 62 patients with GDM who were diagnosed by oral glucose tolerance test (OGTT) and insulin release test from February 2017 to February 2019. According to the severity of the disease, enrolled patients were informed to have appropriate exercise and diet control or Insulin Aspart Injection on this basis until the completion of delivery. By using 50 pregnant women with normal glucose as the control, the fasting plasma glucose (FPG), 1-hour postprandial glucose (1hPG), 2-hour postprandial glucose (2hPG), nocturnal glucose, and glycosylated hemoglobin (HbA1c) levels were compared between the PGDM group and the GDM group before and after treatment; besides, further comparison was made in terms of glucose compliance rate, islet B-cell secretory function, and insulin resistance after treatment. The pregnant women were examined by B-ultrasound at 24 and 26 weeks of gestation to check if the fetus had abnormalities in the central nervous system and the heart. Further B-ultrasound examination was performed at 32 and 37 weeks of gestation to check the problems such as polyhydramnios and stillbirth. In addition, a comparative analysis was carried out in terms of the adverse pregnancy outcomes and complications, associated with the comparison of the results after treatment with control group. Results: After treatment, the levels of FPG, 1hPG, 2hPG, nocturnal glucose, and HbA1c were decreased in the PGDM group and GDM group than those before treatment, especially in the GDM group, with significant difference still when compared with the control group (P < 0.05). Statistical analysis revealed that the blood glucose compliance rate in the GDM group was higher than that in the PGDM group, showing a better therapeutic effect. Fasting insulin (FINS) and homeostasis model assessment index for insulin resistance (HOMA-IR) in the GDM group were significantly higher than those in control group, but lower than those in the PGDM group (P < 0.01), while the level of HOMA-ß was lower in the GDM group than that in the control group and higher than that in PGDM (P < 0.01). Further ultrasound examination revealed the presence of fetal cardiac abnormality, polyhydramnios, stillbirth, and problems, showing a higher incidence in the PGDM group but almost nonexistence in the control group. In addition, the incidence of hypertension, macrosomia, premature rupture of membranes, postpartum hemorrhage, and infection were obviously higher in the PGDM group than those in the GDM group and control group (P < 0.05). Conclusion: Exercise-diet therapy combined with Insulin Aspart Injection can effectively control the blood glucose level of pregnant patients with GDM, improve the pregnancy outcome to a certain extent, and ensure the health of pregnant women and fetus, which is worthy of clinical application.

Effects of Bevacizumab Combined with Chemotherapy on CT, CyFRA21-1, and ProGRP and Prognosis of Lung Cancer Patients under Nursing Intervention.

Objective: Molecular targeted drug therapy and chemotherapy are the main treatments for advanced non-small-cell lung cancer, and the combination of both has advantages in prolonging patients' progression-free survival and overall survival. This study investigated the effects of bevacizumab combined with chemotherapy under nursing intervention on CT, cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), and gastrin-releasing peptide precursor (ProGRP) and prognosis of lung cancer patients. Methods: 102 patients with non-small-cell lung cancer admitted to our hospital from January 2018 to May 2019 were divided into observation group and control group, with 51 cases each. The control group was treated with basic chemotherapy, and the observation group was treated with bevacizumab in combination with the control group, and both groups used nursing interventions. The clinical effects, CYFRA21-1 and ProGRP levels, baseline data, CT parameters, 24-month cumulative survival, and the effects of CYFRA21-1 and ProGRP on long-term survival and lung function were compared. Results: The disease control rate of the observation group was 94.12%, which was significantly higher than that of the control group (76.47%); after 7 d, 30 d, 60 d, and 90 d of treatment, the levels of CYFRA21-1 and ProGRP were statistically downregulated. The difference in lymph node metastasis, lesion diameter, plain Eff-Z, venous stage, and arterial stage normalized iodine concentrations (NIC) was statistically significant; the survival rate at 24 months in the observation group was 74.51% (38/51); the cumulative survival rate at 24 months in the control group was 52.94% (27/51), and the difference was statistically significant (X 2 = 4.980, P = 0.026). The cumulative survival rate at 24 months was significantly lower in patients with high expression of CYFRA21-1 and ProGRP compared with those with low expression of CYFRA21-1 and ProGRP. After treatment, in the observation group, the forceful spirometry (FVC), forceful expiratory volume in one second (FEV1), and FEV1/FVC levels were significantly different from those before treatment and were significantly different from those in the control group. Conclusion: Bevacizumab in combination with standard chemotherapy regimens with nursing interventions could benefit patients with advanced non-small-cell lung cancer and had a good prospect of application.

Analysis of Intervention Effect and Satisfaction of Holistic Nursing after Oral Tumor Resection.

Objective: To explore the intervention effect and satisfaction analysis of holistic nursing after oral tumor resection. Methods: A total of 70 oral tumor patients who underwent surgical treatment in our hospital from April 2020 to September 2021 were randomly divided into two groups, with 35 patients in each group. The control group was given basic oral care, the observation group was given overall oral care, and the actual effects of the two groups of care were compared, including the emotional status, compliance and nursing satisfaction, hospital stay and nursing quality scores, pain level, quality of life, and complications occurred. Results: After nursing, the patients in the observation group had good mood, higher compliance and nursing satisfaction, shorter hospital stay, higher nursing quality and quality of life scores, lower pain level, and lower incidence of complications, when compared with the control group. Conclusion: Holistic nursing has obvious effects on patients after oral tumor surgery, which can relieve patients' negative emotions, improve patients' compliance with treatment, improve their quality of life, and effectively reduce the degree of pain and the occurrence of complications, which is worthy of clinical promotion.

Evaluation of several immune and inflammatory indicators and their association with alopecia areata.

BACKGROUND: Alopecia areata (AA) is an autoimmune disorder and chronic recurrent inflammatory disease that results in non-scarring hair loss. OBJECTIVES: Our aim is to investigate several parameters related to autoimmunity and inflammation in AA patients and to evaluate their association with this disease. METHODS: This study included a total of 672 eligible AA patients and 580 age- and sex-matched healthy individuals who were treated at a third-class hospital in Hefei from January 2016 to May 2020. Data for serum C-reactive protein (CRP), 25-hydroxy vitamin D (25(OH)D), T3, T4, thyroid-stimulating hormone (TSH), thyroid antibodies (TPOAbs and TGAbs), antinuclear antibodies (ANA), complements (C3, C4), and several immunoglobulins (IgA, IgM, and IgG) were collected in this study. RESULTS: Regarding autoimmune-related functional indicators, there were no statistically significant differences between TSH, TGAbs, C3, C4, IgA, IgM, and IgG levels between AA patients and healthy controls. Only T3, T4, TPOAbs, and ANA values were significantly abnormal in the AA group compared with the healthy individuals (p < 0.05). In addition, the mean serum 25(OH)D concentration was significantly lower in the patient group than that in control group (p < 0.05), and serum CRP was significantly increased (p < 0.05). CONCLUSION: Although the etiopathogenesis of AA is not clear, the importance of monitoring the levels of T3, T4, TPOAbs, ANA, and 25 (OH)D in AA cases is indispensable.

Analysis of Epidemic Characteristics and Related Pathogenic Factors of 2726 Cases of Pityriasis Alba.

PURPOSE: To understand the distribution characteristics of onset time, onset age and gender of pityriasis alba (PA) patients in the dermatology clinic of our hospital and to further explore the pathogenesis of the disease to provide a scientific basis for the prevention and treatment of this disease. PATIENTS AND METHODS: The clinical data of 2726 outpatients with PA diagnosed for the first time from January 2016 to December 2020 were collected and descriptively analyzed. RESULTS: The number of patients with PA was less from January to March. The peak was reached in July and August. The number of cases affected by the COVID-19 epidemic in 2020 was significantly lower than that in previous years. Furthermore, the onset age of the patients ranged from 0 to 64 years old, and the median age of the total population was 7 (3, 13) years old, including 1566 males (57.45%) and 1160 females (42.55%). The ratio of male to female was 1.35:1. The number of male patients before 18 years old was higher than that of female patients, especially in the high paroxysmal age group. CONCLUSION: PA can be seen all the year round, and the onset peak of the disease is from July to August every year. It occurs frequently at the age of 1 to 14 before puberty. In the season of high incidence of PA, the protection from sun and moisture retention should be strengthened for infants and adolescents.

A gentamicin-thioctic acid multifunctional hydrogel for accelerating infected wound healing.

Bacterial infections remain a major concern during wound healing and tissue bonding. The excessive proliferation of bacteria will seriously hinder the repair of the wound and even lead to death. Generally, surgical sutures might cause damage to the surrounding tissues and inevitable infection due to the unfixed shape of the wound. Thus, it is urgent to develop novel antibacterial skin dressing with self-healing and strong adhesion properties. Herein, we prepared an antibacterial and self-healable hydrogel with strong adhesion activity through natural small molecules, including thioctic acid TA and gentamicin (GM). The rapid ring-opening-polymerization of the TA (PTA) forms the backbone of macromolecules, and the functional hydrogel was constructed with the crosslinking of GM, termed as G-PTA, which offers hydrogen bonding interactions between the amino and hydroxyl groups of GM and carboxylic group side chains of poly(TA). The synthesized hydrogel exhibited rapid self-healing ability and strong tissue adhesion due to the internal dynamic disulfide bonds and multiple hydrogen bonds. Importantly, the introduction of GM enabled the G-PTA hydrogel to sustainably release antibiotics and exhibit a durative antibacterial effect with the degradation of PTA, which further shorten the therapeutic time and enhance tissue regeneration in a wound infection model. The in vitro and in vivo experiments demonstrate that the G-PTA hydrogel has potential as a surgical antibacterial biological adhesive, especially for bacterial wound infections.

Cholesterol was identified as a biomarker in human melanocytic nevi using DESI and DESI/PI mass spectrometry imaging.

The rapid differentiation between diseased tissue and healthy normal tissue is of great importance for the intraoperative diagnosis. Herein, desorption electrospray ionization (DESI) and DESI/post-photoionization (DESI/PI) mass spectrometry imaging were combined to in situ visualize the distribution of biochemicals within the tissue regions of human melanocytic nevi under the ambient condition with a spatial resolution of around 200 µm. Plenty of polar and nonpolar lipids were found to be specifically distributed in melanocytic nevi with statistical significance and could be used to differentiate the healthy normal tissue and melanocytic nevi. Cholesterol was further confirmed to be a potential biomarker for melanocytic nevi diagnosis by multivariate statistical analysis and immunohistochemistry of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and translocator protein (TSPO) enzymes. This work provides a visual way for the diagnosis of human melanocytic nevi by lipid profiling, which benefits the understanding of the pathological mechanism of melanocytic nevi and provides a new insight to control melanin growth from the synthesis, transport, and metabolism of cholesterol.

Identification and Characterization of Two Novel Alpha-D-Galactosidases from Pedobacter heparinus.

Two putative α-D-galactosidases (α-GALs) belonging to glycosyl hydrolase family 27, and originating from the rather unexplored bacterial strain Pedobacter heparinus, were cloned and biochemically characterized. The recombinant enzymes designated as PhAGal729 and PhAGal2920 showed comparable biochemical properties: the optimum pH values were determined to be pH 5.0 and 5.5, and temperature optima lay between 30°C and 37°C, respectively. Both α-GALs were not dependent on the presence of divalent metal ions, and the addition of EDTA had no influence on enzymatic activity. The activity of both enzymes substantially increased in the presence of Fe3(+) ions. Both enzymes were inhibited by sodium dodecyl sulfate (SDS) and urea. α-GALs from P. heparinus were highly specific in hydrolyzing glycosides with α-1,2/3/4 or α-1,6-linked galactose to other sugars, whereas other glycosides such as α-linked N-acetylgalactosamine, N-acetylglucosamine or glucose residues were not released. Nevertheless, neither PhAGal729 nor PhAGal2920 were able to remove α-linked galactose epitopes from native human erythrocytes. The facile expression and purification procedures in combination with wide substrate specificities make α-GALs from P. heparinus potential candidates for applications in analytical research, and food- and biotechnology.

Complement C4 induces regulatory T cells differentiation through dendritic cell in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. Complement component 4 (C4) has be proved to play a role in pathogenesis of SLE. In the present study, we investigated the effect of C4 on T cells differentiation. METHODS: Thirty SLE patients were included in this study. CD4+ T cells were isolated from healthy subjects, and dendritic cells (DCs) were isolated from healthy subjects or SLE patients. C4 was supplemented to co-incubate with T cells and DCs. RESULTS: Serum C4 concentration was positively correlated with regulatory T cell (Treg) percentage (R(2) = 0.5907, p < 0.001) and TGFß concentration (R(2) = 0.5641, p < 0.001) in SLE patients. Different concentrations of C4 had no effect on T cells differentiation. Co-incubated T cells with DCs and C4 for 7 days, the Treg percentage and TGF-ß concentration were significantly elevated. In addition, pre-treated DCs (from healthy subjects or SLE patients) with C4 and then co-incubated with T cells, the increases of Treg percentage and TGF-ß concentration were also observed. CONCLUSION: C4 takes part in T cells differentiation to Treg cells via DCs.

A simple oligonucleotide biochip capable of rapidly detecting known mitochondrial DNA mutations in Chinese patients with Leber's hereditary optic neuropathy (LHON).

Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease. Clinically, no efficient assay protocols have been available. In this study, we aimed to develop an oligonucleotide biochip specialized for detection of known base substitution mutations in mitochondrial DNA causing LHON and to investigate frequencies of LHON relevant variants in Anhui region of China. Thirty-two pairs of oligonucleotide probes matched with the mutations potentially linked to LHON were covalently immobilized. Cy5-lablled targets were amplified from blood DNA samples by a multiplex PCR method. Two kinds of primary mutations 11778 G > A and 14484 T > C from six confirmed LHON patients were interrogated to validate this biochip format. Further, fourteen Chinese LHON pedigrees and twenty-five unrelated healthy individuals were investigated by the LHON biochip, direct sequencing and pyrosequencing, respectively. The biochip was found to be able efficiently to discriminate homoplasmic and heteroplasmic mtDNA mutations in LHON. Biochip analysis revealed that twelve of eighteen LHON symptomatic cases from the 14 Chinese pedigree harbored the mutations either 11778G > A, 14484T > C or 3460G > A, respectively, accounting for 66.7%. The mutation 11778G > A in these patients was homoplasmic and prevalent (55.5%, 10 of 18 cases). The mutations 3460G > A and 3394T > C were found to co-exist in one LHON case. The mutation 13708G > A appeared in one LHON pedigree. Smaller amount of sampling and reaction volume, easier target preparation, fast and high-throughput were the main advantages of the biochip over direct DNA sequencing and pyrosequencing. Our findings suggested that primary mutations of 11778G > A, 14484T > C or 3460G > A are main variants of mtDNA gene leading to LHON in China. The biochip would easily be implemented in clinical diagnosis.

Psoriasis regression analysis of MHC loci identifies shared genetic variants with vitiligo.

Psoriasis is a common inflammatory skin disease with genetic components of both immune system and the epidermis. PSOR1 locus (6q21) has been strongly associated with psoriasis; however, it is difficult to identify additional independent association due to strong linkage disequilibrium in the MHC region. We performed stepwise regression analyses of more than 3,000 SNPs in the MHC region genotyped using Human 610-Quad (Illumina) in 1,139 cases with psoriasis and 1,132 controls of Han Chinese population to search for additional independent association. With four regression models obtained, two SNPs rs9468925 in HLA-C/HLA-B and rs2858881 in HLA-DQA2 were repeatedly selected in all models, suggesting that multiple loci outside PSOR1 locus were associated with psoriasis. More importantly we find that rs9468925 in HLA-C/HLA-B is associated with both psoriasis and vitiligo, providing first important evidence that two major skin diseases share a common genetic locus in the MHC, and a basis for elucidating the molecular mechanism of skin disorders.

Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population.

Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, P(combined) = 3.15 × 10(-9), odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, P(combined) = 3.0 × 10(-8), OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, P(combined) = 5.90 × 10(-12), OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 × 10(-5), OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis.

Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC.

We conducted a genome-wide association study of generalized vitiligo in the Chinese Han population by genotyping 1,117 cases and 1,429 controls. The 34 most promising SNPs were carried forward for replication in samples from individuals of the Chinese Han (5,910 cases and 9,916 controls) and Chinese Uygur (713 cases and 824 controls) populations. We identified two independent association signals within the major histocompatibility complex (MHC) region (rs11966200, Pcombined=1.48x10(-48), OR=1.90; rs9468925, Pcombined=2.21x10(-33), OR=0.74). Further analyses suggested that the strong association at rs11966200 might reflect the reported association of the HLA-A*3001, HLA-B*1302, HLA-C*0602 and HLA-DRB1*0701 alleles and that the association at rs9468925 might represent a previously unknown HLA susceptibility allele. We also identified one previously undescribed risk locus at 6q27 (rs2236313, Pcombined=9.72x10(-17), OR=1.20), which contains three genes: RNASET2, FGFR1OP and CCR6. Our study provides new insights into the genetic basis of vitiligo.