PSORS1 (psoriasis susceptibility gene 1) is a major susceptibility locus for psoriasis. Several fine-mapping studies have highlighted a 300-kb candidate region of PSORS1 where multiple biologically ...plausible candidate genes were suggested. The most recent study has indicated HLA-Cw6 as the primary PSORS1 risk allele within the candidate region in a Caucasian population. In this study, a family-based association analysis of the PSORS1 locus was performed by analyzing 10 polymorphic microsatellite markers from the PSORS1 region as well as HLA-B, HLA-C and CDSN loci in 163 Chinese families of psoriasis. Five marker loci show strong evidence (P<10(-3)), and one marker locus shows weak evidence (P = 0.04) for association. The haplotype cluster analysis showed that all the risk haplotypes are Cw6 positive and share a 369-kb region of homologous marker alleles which carries all the risk alleles, including HLA-Cw6 and CDSN*TTC, identified in this study. The recombinant haplotype analysis of the HLA-Cw6 and CDSN*TTC alleles in 228 Chinese families showed that the HLA-Cw6(-)/CDSN*TTC(+) recombinant haplotype is clearly not associated with risk for psoriasis (TratioNT = 29:57, p = 0.0025) in a Chinese population, suggesting that the CDSN*TTC allele itself does not confer risk without the presence of the HLA-Cw6 allele. The further exclusion analysis of the non-risk HLA-Cw6(-)/CDSN*TTC(+) recombinant haplotypes with common recombination breakpoints has allowed us to refine the location of PSORS1 to a small candidate region. Finally, we performed a conditional linkage analysis and showed that the HLA-Cw6 is a major risk allele but does not explain the full linkage evidence of the PSORS1 locus in a Chinese population. By performing a series of family-based association analyses of haplotypes as well as an exclusion analysis of recombinant haplotypes, we were able to refine the PSORS1 gene to a small critical region where HLA-C is a strong candidate to be the PSORS1 susceptibility gene.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Genome-wide association studies (GWASs) have identified many genetic variants that are risk factors for numerous immune-mediated diseases. In particular, different immune-mediated diseases have been ...found to share the same susceptibility loci. Therefore, exploring the genetic overlap between atopic dermatitis (AD) and other immune-mediated diseases in more detail may help identify additional shared susceptibility loci among common immune-mediated diseases. Recent evidence suggests that the 11q23.3 locus is a susceptibility locus shared among multiple immune-mediated diseases.
This study was designed to investigated whether SNPs at the chromosome 11q23.3 locus are associated with AD in the Han Chinese population.
In total, 16 SNPs within the 11q23.3 locus were genotyped using TaqMan assays for 1,012 AD cases and 1,362 controls. From these SNPs, we selected rs638893 with an association values of
< 5 × 10
for AD for further analysis in an independent replication study using the Sequenom MassARRAY system to genotype an additional (consisting of 1,288 cases and 1,380 controls). The combined analyses were performed in two stages using a meta-analytical method.
We identified a common variant at 11q23.3 (rs638893), that was significantly associated (
= 1.58 × 10
, OR = 1.22) with AD. The genotype-based association analysis revealed that the recessive model provided the best fit for rs638893.
Our study identified a variant on chromosome 11q23.3 that likely confers susceptibility to AD, thereby advancing our understanding of the genetic basis of this disease.
Dental caries is one of the most common chronic diseases and is caused by acid fermentation of bacteria adhered to the teeth. Streptococcus mutans (S. mutans) utilizes sortase A (SrtA) to anchor ...surface proteins to the cell wall and forms a biofilm to facilitate its adhesion to the tooth surface. Some plant natural products, especially several flavonoids, are effective inhibitors of SrtA. However, given the limited number of inhibitors and the development of drug resistance, the discovery of new inhibitors is urgent. Here, the high-throughput virtual screening approach was performed to identify new potential inhibitors of S. mutans SrtA. Two libraries were used for screening, and nine compounds that had the lowest scores were chosen for further molecular dynamics simulation, binding free energy analysis and absorption, distribution, metabolism, excretion and toxicity (ADMET) properties analysis. The results revealed that several similar compounds composed of benzofuran, thiadiazole and pyrrole, which exhibited good affinities and appropriate pharmacokinetic parameters, were potential inhibitors to impede the catalysis of SrtA. In addition, the carbonyl of these compounds can have a key role in the inhibition mechanism. These findings can provide a new strategy for microbial infection disease therapy.
In vaccinees who were infected with SARS-CoV in 2003, we observed greater antibody responses against spike and nucleoprotein of both SARS-CoV-2 and SARS-CoV after a single dosage of inactivated ...SARS-CoV-2 vaccine. After receiving the second vaccination, antibodies against RBD of SARS-CoV-2 Wuhan, Beta, Delta, and recently emerged Omicron are significantly higher in SARS-CoV experienced vaccinees than in SARS-CoV naïve vaccinees. Neutralizing activities measured by authentic viruses and pseudoviruses of SARS-CoV, SARS-CoV-2 Wuhan, Beta, and Delta are greater in SARS-CoV experienced vaccinees. In contrast, only weak neutralizing activities against SARS-CoV-2 and variants were detected in SARS-CoV naïve vaccinees. By 6 months after the second vaccination, neutralizing activities were maintained at a relatively higher level in SARS-CoV experienced vaccinees but were undetectable in SARS-CoV naïve vaccinees. These findings suggested a great possibility of developing a universal vaccine by heterologous vaccination using spike antigens from different SARS-related coronaviruses.
The MADS-box family gene is a class of transcription factors that have been extensively studied and involved in several plant growth and development processes, especially in floral organ specificity, ...flowering time and initiation and fruit development. In this study, we identified 69 candidate MADS-box genes and clustered these genes into five subgroups (Mα: 11; Mβ: 2; Mγ: 14; Mδ: 9; MIKC: 32) based on their phylogenetical relationships with
. Most
genes within the same subgroup showed a similar gene structure and highly conserved motifs. Chromosomal distribution analysis revealed that all the
genes were evenly distributed in 10 chromosomes. Additionally, the cis-acting elements of promoter, physicochemical properties and subcellular localization were also analyzed. This study provides a comprehensive analysis of MADS-box genes in
and lays the foundation for further functional research.
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.
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.
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)).
These results showed that two common susceptibility loci (NFKBIA and IL28RA) are shared by psoriasis and SLE in the Chinese Han population.
Acne inversa (hidradenitis suppurativa) is a chronic relapsing inflammatory skin disease characterized by recurrent draining sinuses and abscesses, predominantly in skin folds that carry terminal ...hairs and apocrine glands. The genetic basis for this disease is unknown. In this study, we performed a genome-wide scan in a four-generation Chinese family to map the chromosome location of the responsible gene. We first identified a locus at chromosome 1p21.1–1q25.3 with the maximum logarithm of odds (LOD) score of 3.26 at the marker D1S2624 (at recombination fraction=0.00). The other two-point LOD scores ≥3 were observed at markers D1S2695, D1S2726, D1S252, and D1S2777. Haplotype analysis localized this locus to a 76Mb region flanked by D1S248 and D1S2711. This is the first locus for the inversa acne and will be a starting point towards understanding the molecular mechanisms of this disease.
To identify susceptibility loci for vitiligo, we extended our previous vitiligo genome-wide association study with a two-staged replication study that included 6,857 cases and 12,025 controls from ...the Chinese Han population. We identified three susceptibility loci, 12q13.2 (rs10876864, Pcombined=8.07 × 10−12, odds ratio (OR)=1.18), 11q23.3 (rs638893, Pcombined=2.47 × 10−9, OR=1.22), and 10q22.1 (rs1417210, Pcombined=1.83 × 10−8, OR=0.88), and confirmed three previously reported loci for vitiligo, 3q28 (rs9851967, Pcombined=8.57 × 10−8, OR=0.88), 10p15.1 (rs3134883, Pcombined=1.01 × 10−5, OR=1.11), and 22q12.3 (rs2051582, Pcombined=2.12 × 10−5, OR=1.14), in the Chinese Han population. The most significant single-nucleotide polymorphism in the 12q13.2 locus is located immediately upstream of the promoter region of PMEL, which encodes a major melanocyte antigen and has expression loss in the vitiligo lesional skin. In addition, both 12q13.2 and 11q23.3 loci identified in this study are also associated with other autoimmune diseases such as type 1 diabetes and systemic lupus erythematosus. These findings provide indirect support that vitiligo pathogenesis involves a complex interplay between immune regulatory factors and melanocyte-specific factors. They also highlight similarities and differences in the genetic basis of vitiligo in Chinese and Caucasian populations.
A series of cation‐exchanged RHO zeolites, including H‐RHO, Li‐RHO, Na‐RHO, K‐RHO, Cs‐RHO, Cd‐RHO and Pb‐RHO, were prepared, and the samples were characterised by X‐ray diffraction, scanning electron ...microscopy, energy dispersive X‐ray spectroscopy, thermogravimetric analysis, inductive coupled plasma emission spectrometer and N2‐BET. The CO2 and CO adsorption behaviours of the samples were measured at 298 K and 0–10 bar. The Langmuir equation was used to fit adsorption isotherms to compare the separation effect of these RHO zeolites. The results show that extra‐framework cations can effectively adjust the pore size of RHO. Not only it depends on the size of the cation radius, but other factors also play an important role, such as the position of the cation. Besides, compared with CHA structure, RHO structure has better CO2/CO separation performance. In all researched cationic forms of RHO, Li‐RHO, Cd‐RHO and Pb‐RHO have excellent CO2/CO separation effects. Among them, the pore size of Cd‐RHO is significantly reduced, thereby restricting the entry of CO more effectively, ultimately leading to greater shape selectivity. Cd‐RHO not only has the highest CO2 saturated adsorption capacity and CO2 working capacity but also has relatively excellent CO2/CO selectivity, resulting in the sorbent selection parameter (S) is also the largest.
Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To further advance gene discovery, we extended our genome-wide association study data set of 1,139 cases and 2,234 ...controls and replicated two independent cohorts of 7,200 cases and 10,491 controls. We identified the missense variant rs2303138 (p.Ala763Thr) within the LNPEP gene associated with psoriasis (Pcombined=1.83 × 10-13, odds ratio=1.16) and validated four previously reported genes: IL28RA, NFKBIA, TRAF3IP2, and CARD14 (9.74 × 10-11⩽P⩽9.37 × 10-5), which confirmed the involvement of the nuclear factor-κB signaling pathway in psoriasis pathogenesis. LNPEP, also named insulin-responsive aminopeptidase, was identified as an angiotensin IV receptor. Protein function prediction suggested that this missense variant of LNPEP was most likely deleterious. Expression analysis showed that LNPEP was significantly downregulated in psoriatic lesions compared with the control skin (P=1.44 × 10-6) and uninvolved patient skin (P=2.95 × 10-4). Pathway analysis indicated that LNPEP was involved in the renin–angiotensin system, which also has a key role in cardiovascular disease and diabetes. These results provided genetic evidence that psoriasis might share common mechanisms with hypertension and diabetes, which was consistent with clinical observations. Our study identified a genetic susceptibility factor and provided genetic evidence of insight into psoriasis pathogenesis with the involvement of the renin–angiotensin system pathway.
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