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A girl, aged 11 years, was admitted due to recurrent rash on the whole body and mucosa for 10 years, and typical rash was erythema at the perioral region, hand-foot joints, vulva, and perianal region, with blisters, erosions, and ulcers on the erythema. The girl was improved after zinc supplementation. Her younger brother had similar rash and medical history. The histopathological examination showed epidermal parakeratosis with mild hyperkeratosis, severe spongiform edema of the stratum corneum, significant proliferation of acanthocytes, and vacuolation of keratinocytes. The genetic testing revealed that both the girl and her younger brother had a homozygous mutation of c.1456(exon9)delG in the SLC39A4 gene, and thus the girl was diagnosed with acrodermatitis enteropathica. It is concluded that for children with recurrent rash on the limbs and at the perioral region, genetic testing should be performed as early as possible to make a confirmed diagnosis, and a sufficient dose of zinc supplementation should be given, while the levels of trace elements such as blood zinc should be regularly monitored.

Background Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China. Methods Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world. Results In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million. Conclusions The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations.

A girl, aged 22 months, attended the hospital due to recurrent vulvar rashes for more than half a year. Skin biopsy showed Langerhans cell histiocytosis, and evaluation of systemic conditions showed no systemic involvement. Therefore, the girl was diagnosed with Langerhans cell histiocytosis (skin type). In conclusion, for rashes on the vulva alone, if there are no specific clinical manifestations, the possibility of Langerhans cell histiocytosis should be considered after molluscum contagiosum, sexually transmitted diseases, and Fordyce disease are excluded.

Crigler‐Najjar syndrome type 1 (CN1) is an autosomal recessive disease caused by a marked decrease in uridine‐diphosphate‐glucuronosyltransferase (UGT1A1) enzyme activity. Delivery of hUGT1A1‐modRNA (a modified messenger RNA encoding for UGT1A1) as a lipid nanoparticle is anticipated to restore hepatic expression of UGT1A1, allowing normal glucuronidation and clearance of bilirubin in patients. To support translation from preclinical to clinical studies, and first‐in‐human studies, a quantitative systems pharmacology (QSP) model was developed. The QSP model was calibrated to plasma and liver mRNA, and total serum bilirubin in Gunn rats, an animal model of CN1. This QSP model adequately captured the observed plasma and liver biomarker behavior across a range of doses and dose regimens in Gunn rats. First‐in‐human dose projections made using the translated model indicated that 0.5 mg/kg Q4W dose should provide a clinically meaningful and sustained reduction of >5 mg/dL in total bilirubin levels.

The objective of this study was to systemically and comprehensively evaluate the associations between smoking and disease outcomes in patients with ankylosing spondylitis (AS). Information on smoking, clinical features, and sociodemographic characteristics was collected by a questionnaire administered directly to the patient. Group differences were analyzed by t test or chi-square test. Logistic regression analysis was conducted with the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), C-reactive protein, and erythrocyte sedimentation rate as the dependent variables and different stratification of smoking duration, smoking intensity, and cumulative smoking as independent variables. In order to compare our results with previous studies, meta-analysis was performed to calculate standardized mean difference (SMD) for relationship between outcomes and smoking status. A total of 1178 AS patients were analyzed. Compared with non-smokers, the risk of having active disease (BASDAI ≥ 4) was higher in patients who smoked at least 15 years, or 15 cigarettes per day, or 15 pack-years (OR = 1.70 [1.06, 2.73], 1.75 [1.08, 2.82], and 1.97 [1.06, 3.67], respectively); and smokers had increasing risk of BASDAI ≥ 4 with increasing years of smoking, or cigarettes per day, or pack-years (p-trend = 0.010, 0.008 and 0.006, respectively). The risk of having active disease was higher in patients who smoked at least 15 cigarettes per day or 15 pack-years (OR = 1.74 [1.06, 2.84] and 2.89 [1.56, 5.35], respectively), with increasing number of cigarettes per day and pack-years. Smokers had an increased risk of BASFI ≥ 4 (p-trend = 0.040 and 0.007, respectively). By meta-analysis, current, former and ever smokers had significantly higher BASDAI (SMD = 0.34 [0.18, 0.48], 0.10 [0.01, 0.19], and 0.27 [0.20, 0.34], respectively) and BASFI (SMD = 0.35 [0.16, 0.55], 0.30 [0.22, 0.39], and 0.35 [0.21, 0.50], respectively) compared to non-smokers. Smoking is a risk factor for greater disease activity and worse functioning in AS patients.

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease. The 5q22.1 region was found to have an association with AD in our previous genome-wide association study (GWAS). Objective To identify the AD susceptibility gene in 5q22.1 and observe its expression in AD tissues. Methods Suggestive indels from the GWAS data were genotyped in 3013 AD patients and 5075 controls from the Chinese Han population with the SequenomMassArray system. Association, Bayesian and bioinformatics analyses were used to identify possible causal indels and genes in the 5q22.1 region. Immunohistochemistry (IHC) was performed to observe protein expression in the tissues. PLINK 1.07 software was used for all statistical analyses. Results The genotyping and association analysis showed that six deletions and four SNPs were associated with AD (P Conclusions The study indicates that TMEM232 in the 5q22.1 region is the causal gene for AD in the Chinese Han population.

The study aimed to determine whether unique clinical patterns of AS may exist in China, specifically to explore the different clinical manifestations caused by gender, HLA-B27 status, and age at disease onset. The multicenter cross-sectional survey was conducted and 1251 patients were enrolled across China, representing a broad spectrum of Chinese AS patients. The mean age at onset and diagnosis were 29.2 (11.4) and 33.5 (12.6) years, respectively. The male/female ratio was 2.7:1. Acute anterior uveitis (AAU) was experienced in 10.3% of AS patients and 9.1% patients had juvenile-onset AS (JoAS). Men were significantly younger at onset and diagnosis and showed a higher frequency of HLA-B27 positivity, JoAS, and AAU than women. HLA-B27-positive patients had a younger age of onset than HLA-B27-negative patients. HLA-B27-positive patients were nearly three times as likely to develop AAU than negative patients (P = 0.04). JoAS patients had a family history of AS more often than adult-onset AS (AoAS) patients, and 4.9% of JoAS patients underwent surgical treatments, a rate more than six times that of AoAS patients (P = 0.01). Men had higher levels of C-reactive protein than women, as did HLA-B27 positives compared to negative patients, and JoAS compared to AoAS (all P

A girl, aged 15 months, attended the hospital due to recurrent skin erythema, blisters, and desquamation for more than 7 months. Giemsa staining and immunohistochemical staining showed mast cell infiltration and degranulation. Hematoxylin staining showed spinous layer edema and blister formation under the epidermis, with a large amount of serous fluid and a small number of inflammatory cells in the blister. Marked edema was observed in the dermis, with diffused mononuclear cell infiltration. The girl was diagnosed with mastocytosis. Mastocytosis should be considered for children with recurrent skin erythema and blisters.

// Santasree Banerjee 1,* , Dongzhu Lei 2,* Shengran Liang 1,* , Li Yang 3,* , Saijun Liu 1 , Zhu Wei 4 and Jian Ping Tang 4,* 1 BGI-Shenzhen, Shenzhen, China 2 Center of Prenatal Diagnosis, ChenZhou No.1 peoples hospital, Hunan, China 3 Biological therapy center, The Third Affiliated Hospital, Sun-Yet-San University, Guangzhou, China 4 Department of dermatology, Hunan Children’s Hospital, Hunan, China * These authors have contributed equally to the manuscript Correspondence to: Jian Ping Tang, email: // Keywords : neurofibromatosis type 1, next generation sequencing, novel mutation, NF1 gene, mutational screening Received : July 10, 2016 Accepted : December 06, 2016 Published : December 14, 2016 Abstract Neurofibromatosis type 1 (NF1) is an autosomal dominant, multi-system, neurocutaneous disorder, manifested with neurofibromas and Cafe´-au-lait spots. Germline mutations in NF1 gene are associated with Neurofibromatosis type 1. NF1 gene encodes neurofibromin, a RAS-specific GTPase activating protein. In our study, we present a clinical molecular study of four Chinese probands with NF1 from four unrelated families, showing extreme phenotypic variation with rare phenotype. In family 1, the proband is a 16 months old girl with multiple cafe-au-lait spots throughout her whole body. In family 2, the proband is a 6 months old girl with several cafe-au-lait spots mostly in her trunk and in lower limbs. In family 3, the proband is a 4 months old boy with several cafe-au-lait spots, tibial pseudarthrosis, and chronic iron deficiency anemia. In family 4, the proband is a 14 years old boy with multiple cafe-au-lait spots of variable sizes. Targeted exome capture based next generation sequencing and Sanger sequencing identified a novel mutation and three previously reported mutations in these four probands. These four mutations in NF1 gene were causing disease phenotypes in these four probands and was absent in unaffected family members and in healthy controls. According to the variant interpretation guideline of American College of Medical Genetics and Genomics (ACMG), these four mutations, are classified as “likely pathogenic”. Our result expands the mutational spectrum of the NF1 gene associated with neurofibromatosis type1.

Primary Hyperoxaluria Type 1 (PH1) is an autosomal recessive disorder of glyoxylate metabolism. Loss of alanine glyoxylate aminotransferase (AGT) function to convert intermediate metabolite glyoxylate to glycine causes the accumulation and reduction of glyoxylate to glycolate, which eventually is oxidized to oxalate. Excess oxalate in PH1 patients leads to the formation and deposition of calcium oxalate crystals in the kidney and urinary tract. Oxalate crystal deposition causes a decline in renal function, systemic oxalosis, and eventually end-stage renal disease and premature death. mRNA-based therapies are a new class of drugs that work by replacing the missing enzyme. mRNA encoding AGT has the potential to restore normal glyoxylate to glycine metabolism, thus preventing the buildup of calcium oxalate in various organs. Panels of codon-optimized AGT mRNA constructs were screened in vitro and in wild-type mice for the production of a functional AGT enzyme. Two human constructs, wild-type and engineered AGT (RHEAM), were tested in Agxt-/- mice. Repeat dosing in Agxt-/- mice resulted in a 40% reduction in urinary oxalate, suggesting therapeutic benefit. These studies suggest that mRNA encoding AGT led to increased expression and activity of the AGT enzyme in liver that translated into decrease in urinary oxalate levels. Taken together, our data indicate that AGT mRNA may have the potential to be developed into a therapeutic for PH1.

Purpose: To explore the role of TWEAK in tumor growth and antitumor immune response and the activity and mechanism of RG7212, an antagonistic anti-TWEAK antibody, in tumor models. Experimental Design: TWEAK-induced signaling and gene expression were explored in tumor cell lines and inhibition of these effects and antitumor efficacy with RG7212 treatment was assessed in human tumor xenograft-, patient-derived xenograft, and syngeneic tumor models and phase I patients. Genetic features correlated with antitumor activity were characterized. Results: In tumor cell lines, TWEAK induces proliferation, survival, and NF-κB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. TWEAK-inducible CD274, CCL2, CXCL-10 and -11 modulate T-cell and monocyte recruitment, T-cell activation, and macrophage differentiation. These factors and TWEAK-induced signaling were decreased, and tumor, blood, and spleen immune cell composition was altered with RG7212 treatment in mice. RG7212 inhibits tumor growth in vivo in models with TWEAK receptor, Fn14, expression, and markers of pathway activation. In phase I testing, signs of tumor shrinkage and stable disease were observed without dose-limiting toxicity. In a patient with advanced, Fn14-positive, malignant melanoma with evidence of tumor regression, proliferation markers were dramatically reduced, tumor T-cell infiltration increased, and tumor macrophage content decreased. Antitumor activity, a lack of toxicity in humans and animals and no evidence of antagonism with standard of care or targeted agents in mice, suggests that RG7212 is a promising agent for use in combination therapies in patients with Fn14-positive tumors. Clin Cancer Res; 19(20); 5686–98. ©2013 AACR.

A two-month-old boy visited the hospital due to unexpected cutaneous purpura and thrombocytopenia for 2 days. The physical examination revealed a purple mass on the back. The soft tissue color Doppler ultrasound showed rich blood signals in the tissue, and the results of bone marrow puncture indicated an increased number of megakaryocytes. After the treatment with hormone and gamma globulin, the platelet count rapidly increased and maintained at a normal level. Meanwhile, the boy was given oral administration of propranolol. He was followed up for 4 months and the volume of the mass on the back was reduced significantly. He had a definite diagnosis of hemangioma and immune thrombocytopenia. As for the patients with hemangioma complicated by thrombocytopenia, knowledge of Kasabach-Merritt syndrome should be enhanced and there should be a clarification of the association between thrombocytopenia and hemangioma. There should also be an alertness for thrombocytopenia of other causes.

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.

R411 is a dual alpha4beta1-alpha4beta7 integrin antagonist under development for the treatment of chronic asthma. The objective of this study was to investigate the pharmacokinetics and safety of R411 and its active metabolite, RO0270608, in humans. A 3-part phase I trial was conducted in 132 healthy volunteers: (1) 12 subjects received 200 mg R411 as a single oral dose or 100 mg RO0270608 as an intravenous infusion in a 1-sequence crossover design; (2) 7 groups of 10 subjects received 1 of 7 single oral doses of R411 (10-1200 mg) in a parallel, placebo-controlled, ascending adaptive dose design; and (3) 5 groups of 10 subjects each received repeated oral qd doses of R411 (50-900 mg) for up to 3 weeks in a parallel, placebo-controlled, ascending adaptive dose design. The absolute bioavailability of RO0270608 (mean +/- standard deviation) after oral administration of R411 was 27% +/- 4%, and the terminal half-life was 7.33 +/- 2.29 hours. After IV infusion of RO0270608, total clearance (mean +/- standard deviation) was 19.4 +/- 7.1 L/h, and the volume of distribution was 93.1 +/- 36.1 L. After single ascending oral doses of R411, area under the concentration-time curve from 0 to infinity of active metabolite RO0270608 increased proportionally from 150 to 1200 mg (P > .05). Following repeated administration, the oral clearance was independent of time. No drug accumulation was observed, and no safety concerns were revealed up to a dose of 900 mg after up to 3 weeks of treatment.

To investigate the correlation between carbapenem consumption and rates of antimicrobial resistance in Acinetobacter baumannii, carbapenem consumption was expressed as defined daily dose based on the World Health Organization (WHO) anatomical therapeutic chemical classification index. Clinical isolates from 2001-2009 were collected and analyzed using WHONET 5.4 software. Results show that the consumption of imipenem/cilastatin, meropenem, and total carbapenem is significantly correlated with imipenem resistance in A baumannii (r = 0.818, P = .007; r = 0.817, P = .007; r = 0.827, P = .006). Furthermore, total carbapenem consumption is significantly correlated with meropenem resistance in A baumannii (r = 0.900, P = .037). In addition, consumption of imipenem/cilastatin, meropenem, and total carbapenem is associated with A baumannii resistance to piperacillin-tazobactam, ceftazidime, cefepime, amikacin, and levofloxacin. These drugs are mainly β-lactams, aminoglycosides, and fluoroquinolones. The imipenem and meropenem resistance rates are significantly correlated with resistance rates to numerous antimicrobial drugs (eg, β-lactams, aminoglycosides, and fluoroquinolones) in A baumannii. Therefore, increased consumption of carbapenem may contribute to the development of resistance in A baumannii to imipenem, meropenem, and other antimicrobial drugs. Cross-resistance possibly occurs among imipenem/cilastatin and meropenem, as well as with β-lactams, aminoglycosides, and fluoroquinolones.

To investigate the allergens of various allergic diseases in children.Serum levels of Fx5E, Phadiatop and specific IgE were measured by the UniCAP100 System in 3 504 children with allergic diseases.The positive rate of aeroallergens was obviously higher than that of food allergens in children with allergic rhinitis, allergic conjunctivitis, asthma and papular urticaria. In contrast, the positive rate of food allergens was obviously higher than that of aeroallergens in children with Henoch-Schonlein purpura and digestive diseases. The serum specific IgE level of aeroallergens was higher than that of food allergens. The dust and mite specific IgE levels reached to grade 6, while the food allergen specific IgE levels were lower than grade 3.Aaeroallergens or food allergens vary remarkably in different allergic diseases in children. The level of specific IgE of aeroallergens is higher than that of food allergens.

This study examined the expression of Toll-like receptors (TLR) in peripheral blood mononuclear cells (PBMC) and serum levels of IL-6, IL-10 and TNF-alpha in children with recurrent herpes simplex, in order to investigate the role of TLR2 and TLR9 in recurrent herpes simplex.The expression of TLR2 and TLR9 in PBMC was examined by flow cytometer, and serum levels of IL-6, IL-10 and TNF-alpha were detected using ELISA in 22 children with recurrent herpes simplex and in 13 age-matched healthy volunteers.The expression of both TLR2 and TLR9 obviously increased in children with recurrent herpes simplex compared with that in healthy controls (p0.01). Serum levels of IL-6 and IL-10 increased, while serum TNF-alpha levels decreased significantly in children with recurrent herpes simplex compared with those in healthy controls (p0.01). There were positive correlations between TLR2 and TLR9 expression and serum IL-6 and IL-10 levels in children with recurrent herpes simplex (p0.01).TLR2 and TLR9 in PBMC may participate in the recognition of herpes simplex virus and activate the signal pathway of TLR in children with recurrent herpes simplex. The production and release of IL-6 and IL-10 might be mediated by TLR2 and TLR9.

To investigate the distribution of allergens in children with allergic disease in Changsha.Total IgE and specific IgE against some allergens were examined by the AllergyScreen system in the sera of 437 children from Changsha with allergic disease.The positive rates of total IgE and special IgE were 68.9% and 69.1% respectively. Dermatophagoides farina, beef, mutton, milk and fur of cats and dogs were found as common allergens. The IgE positive rate against dermatophagoides farina was the highest in children with allergic rhinitis (86.0%), followed by in those with atopic dermatitis (41.2%), eczema (27.6%) and urticaria (20.0%). Serum IgE was positive against the fur of cats and dogs in 23.5% of children with atopic dermatitis and in 18.1% of children with eczema. The IgE positive rate was lower in children with urticaria and allergic rhinitis (10.0% and 8.7% respectively). IgE positive rates against milk, beef and mutton were high in the above four allergic diseases (range: 14.0%-24.0%), but no significant differences were observed for the IgE positive rate among the four allergic diseases. The IgE positive rate to inhalant allergens in children at ages of less than 3 years was markedly higher than that in children at ages of more than 3 years (p0.01).Allergic diseases are mainly mediated by allergens. Allergens, especially dermatophagoides farina, fur of cats and dogs, beef, mutton and milk, play an important role in childhood allergic diseases in Changsha.

To detect low copy number of DNA samples by using a newly launched commercial miniSTR detection kit (MiniFiler) in forensic practice.Low concentration and/or challenged forensic DNA samples were analyzed according to protocols provided by the manufacturer (Applied Biosystems, Foster City, USA).DNA samples as low as 10 pg could be amplified by MiniFiler kit, and the optimal DNA quantity was 40 pg or above.MiniFiler kit can be used for analysis of low copy number STR.

To study genetic polymorphisms of 20 Y-chromosomal short tandem repeats (STR) in Chaoshan Han population, and to evaluate their value in forensic science.Twenty Y-specific STR loci (DYS434, Y-GATA-A10, Y-GATA-H4, DYS438, DYS439, DYS443, DYS444, DYS446, DYS447, DYS448, DYS456, DYS458, DYS460, DYS520, DYS531, DYS557, DYS622, DYS630, DYS635 and DYS709) were amplified by using three fluorescence-labeled multiplex PCR systems and were analyzed by ABI310 genetic analyzer. One hundred and fifty-eight unrelated male individuals of Han population in Chaoshan area were investigated to determine the distribution of allele frequencies and haplotype.The Y-STR multiplexes developed had followed the published nomenclature and ISFG guidelines for STR analysis. Gene diversity ranged from 0.2506 at DYS434 to 0.8034 at DYS447. A total of 157 different haplotypes were observed, and among these, 156 were unique, while 1 was found for two times. The haplotype diversity value calculated from all 20 loci combined was 0.999998. None of Y-STR allele mutation was observed in the 30 father/ son pairs confirmed by autosomal STR analysis.The results indicate that the 20 Y-STR loci are highly polymorphic and fathership genealogy inheritance are stable. The three fluorescence-labeled multiplex amplification systems that we constructed are suitable for forensic individual identification and paternity testing in Chaoshan area.

This study was designed to investigate the value of serologic examination in the diagnosis of childhood herpes simplex virus (HSV) infection.Serum samples were collected from 2 436 outpatients and inpatients. The samples were divided into two groups. Group 1 consisted of 321 samples which were assayed for HSV-1 IgG, HSV-1 IgM, HSV-2 IgG or HSV-2 IgM antibody using herpes simplex virus antibody kits between January 2003 and November 2005. Group 2 consisted of 2115 samples which were assayed for HSV-2 IgG and IgM antibodies by TORCH testing between October 2004 and November 2005.In Group 1, the total seroprevalence of HSV infection was 44.6%, with 38.9% being HSV-1 positive and 15.9% HSV-2 positive; HSV-IgM positivity was found in 41.1% and 25.5% were HSV-IgG positive; HSV-1 seroprevalence significantly increased with age (P0.05). In Group 2 the seroprevalence of HSV-2 infection was 1.9%; all of the samples were HSV-2 IgG positive.HSV serologic examination is useful in the diagnosis of HSV infection in children.

Six hundred thirty-five patients underwent oral propranolol treatment for infantile hemangioma. The efficacy rate was 91.2% and 162 of the patients recovered completely. No significant adverse effects were observed and the overall incidence of adverse effects was 2.1%.

To observe whether single nucleotide polymorphisms (SNPs) within the OLF1/EBF-associated zinc finger protein (OAZ) gene are associated with lupus nephritis (LN) susceptibility in Chinese population.Eight SNPs located around the positive microsatellite marker D16S517 within OAZ gene with relatively high heterozygosity were chosen for genotyping on 184 systemic lupus erythromatosus (SLE) patients, including 101 non-LN patients and 83 LN patients, and 286 normal controls using TaqMan MGB allelic discrimination method. Data were collected by SDS 2.0 software. Haplotypes and their frequencies were constructed and estimated, and linkage disequilibrium analysis between pairs of SNPs was evaluated by calculating the D Prime using Helixtree program. Case-control study was performed between the SLE, LN, and non-LN groups and normal control group.(1) The frequency of SNP rs1344531 T allele was 47.0% in the SLE patients, significantly higher than that in the controls [38.1%,; chi(2) = 7.300, P = 0.008, OR (95% CI) = 1.441 (1.105 - 1.878)], which showed that the frequency of SNP rs1344531 T allele is associated with SLE susceptibility. The genotypic distribution of SNP rs1344531(CC/CT/TT) differed significantly between the SLE patients (25.5%/54.9%/19.6%) and normal controls (38.1%/47.6%/14.3%) (chi(2) = 8.394, P = 0.015). The CC genotype frequency of the SLE patients was 25.5%, significantly lower than that of the normal controls [38.1%; chi(2) = 7.976, P = 0.005, OR (95% CI) = 0.557 (0.370 - 0.838)] (2) The SNP rs1344531 T allele frequency of the SLE patients was 53.0%, significantly higher than that of the normal controls [38.1%; chi(2) = 11.769, P = 0.001, OR (95% CI) = 1.832 (1.293 - 2.596)], which showed an associated between SNP rs1344531 T allele frequency and LN susceptibility. The genotypic distribution of SNP rs1344531 (CC/CT/TT) differed significantly between the LN patients (22.9%/48.2%/28.9%) and the normal controls (38.1%/47.6%/14.3%) (chi(2) = 12.065, P = 0.002). The CC genotype frequency of the LN patients was 22.9%, significantly lower than that of the normal controls (38.1%) [chi(2) = 6.578, P = 0.013, OR (95% CI) = 0.481 (0.274 - 0.848)]. The TT genotype frequency of the LN patients was 28.9%, significantly higher than that of the normal controls (14.3%) [chi(2) = 9.423, P = 0.003, OR (95% CI) = 2.431 (1.363 - 4.334)]. No statistical significance was observed between the non-LN patients and normal controls in TT genotype frequency. (3) The frequencies of haplotypes containing rs1344531:rs1420676-rs1344531(C-T) [chi(2) = 11.731, P = 0.001, OR (95% CI) = 1.867 (1.302 - 2.676)], rs3803665-rs1420676-rs1344531(C-C-T) [chi(2) = 8.876, P = 0.004, OR (95% CI) = 1.772 (1.213 - 2.589)], and rs2292155-rs3803665-rs1420676-rs1344531(C-C-C-T) [chi(2) = 9.962, P = 0.002, OR (95% CI) = 1.915 (1.274 - 2.880)] were all significantly higher in the LN patients in comparison with the normal control group (41.0% versus 27.1%; 33.3% versus 21.8%; and 27.0% versus 16.2%); while the frequencies of other haplotypes: rs1344531-rs2080353(C-A) [chi(2) = 8.06, P = 0.005, OR (95% CI) = 0.603 (0.424 - 0.856)], rs1344531-rs2080353-rs933564 (C-A-G) [chi(2) = 7.929, P = 0.006, OR (95% CI) = 0.602 (0.422 - 0.859)] were significantly lower than those of the normal control group (39.5% versus 52.2%, and 36.6% versus 49.2%), which produced additional support for such association.SNP rs1344531 and some haplotypes containing SNP rs1344531 within OAZ are significantly associated with LN susceptibility. Genetic variants of the OAZ gene are involved in the pathogenesis of LN.

To investigate the expression levels of interferon (IFN)-alpha, -beta, -omega and -gamma genes and proteins in the peripheral blood of patients with systemic lupus erythematosus (SLE), and to evaluate any possible connections between these expression levels with clinical features.144 SLE patients, 27 non-SLE patients with rheumatisms and 59 normal controls were recruited for the research, and all subjects were drawn blood to isolate plasma and elute total RNA. SYBR Green Dye based real-time quantitative PCR method was used to compare the expression levels of 4 IFNs in patients with SLE and those in the controls. The significance for the correlation of these expression levels and disease activity and specificity was studied.(1) mRNA expression levels of all 4 IFNs in SLE patients were remarkably lower than those observed in normal controls (P0.01 in all); IFN-alpha expression levels in SLE patients were increased than those observed in non-SLE group (P0.01). (2) The expression levels of all 4 IFNs in active SLE patients were similar to those observed in inactive SLE patients (P0.05 in all), and expression levels of all 4 IFNs in patients with SLE were not correlated with involvements of kidney, lung, brain, blood. (3) IFN score in SLE patients was remarkably lower than that observed in normal controls (P0.01). (4) The expression levels of all 4 IFNs in both SLE patients and normal controls were positively correlated with each other (P0.01 in all). (5) Protein levels of IFN-alpha, IFN-beta and IFN-omega in patients with SLE were similar to those observed in normal group (P0.05 in all), protein level of IFN-alpha in active SLE group was apparently elevated than in inactive SLE group (P0.01), and protein level of IFN-gamma has a trend to increase in SLE group than in normal group.Decreased expression levels of IFN-alpha, -beta, -omega and -gamma have implicated significance in the determination of SLE disease specificity, of which IFN-alpha is the best. Lower expression level of IFN score has also significance in the determination of SLE disease specificity. Higher protein level of IFN-alpha is helpful to judging SLE disease activity.