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Background Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant disorder characterised by coarse, wiry, twisted hair developed in early childhood and subsequent progressive hair loss. MUHH is a genetically heterogeneous disorder. No gene in 1p21.1–1q21.3 region responsible for MUHH has been identified. Methods Exome sequencing was performed on two affected subjects, who had normal vertex hair and modest alopecia, and one unaffected individual from a four-generation MUHH family of which our previous linkage study mapped the MUHH locus on chromosome 1p21.1–1q21.3. Results We identified a missense mutation in EPS8L3 (NM_024526.3: exon2: c.22G->A:p.Ala8Thr) within 1p21.1–1q21.3. Sanger sequencing confirmed the cosegregation of this mutation with the disease phenotype in the family by demonstrating the presence of the heterozygous mutation in all the eight affected and absence in all the seven unaffected individuals. This mutation was found to be absent in 676 unrelated healthy controls and 781 patients of other disease from another unpublished project of our group. Conclusions Taken together, our results suggest that EPS8L3 is a causative gene for MUHH, which was helpful for advancing us on understanding of the pathogenesis of MUHH. Our study also has further demonstrated the effectiveness of combining exome sequencing with linkage information for identifying Mendelian disease genes.

Asthma is a complex inflammatory disorder of the airways, and research on alternative therapeutic strategies has attracted attention. This study aimed at hypersusceptibility and toxicity of recombinant human phospholipase D2 (rhPLD2) in guinea pigs. We determined the behavioral responses in the model of immediate hypersensitivity animals and changes of eosinophil levels following use of the drugs. Special attention was given to the effects of rhPLD2 in vivo on the guinea pig with chronic persistent asthma and the mechanism involved.To investigate the effect of rhPLD2 on the expression of protein kinase C (PKC), and to examine the activity of signal transducer and activator of transcription 1 and 5a in the lung of the guinea pig with chronic asthma. Guinea pigs with chronic asthma were divided into five groups: a saline group, a dexamethasone 5.0 mg group, and rhPLD2 (1.5, 2, or 3 mg) groups. Non-sensitized animals were as normal control group. PKC expression was measured by immunohistochemistry, alterations of STAT1 and STAT5a were detected by TransAM transcription factor assay kits.rhPLD2 (3.0 mg) decreased PKC expression to baseline and inhibited STAT1 activity compared with that of the saline group (p 0.01).The rhPLD2 may suppress the chronic inflammatory reaction through down-regulating PKC expression and STAT1/STAT5a activity in the lung. The rhPLD2 may be a suitable therapeutic target for asthma.

Systemic lupus erythematosus (SLE) is an autoimmune disease influenced by genetic and environmental factors. Recently, single nucleotide polymorphisms (SNPs) in the region of B lymphoid tyrosine kinase (BLK) have been shown to be associated with SLE in Caucasian population. In this paper, we genotyped SNP rs2248932 in 1,396 SLE patients of Chinese Han and 4,362 ethnically matched control subjects by using the Sequenom MassArray system. We confirmed that SNP rs2248932 in BLK gene was significantly associated with SLE (P = 1.41 x 10(-8) for the allele frequency, Odds ratio [OR] = 0.74, 95% confidence interval (CI): 0.66-0.82).The association of BLK in Chinese SLE patients was consistent with a dominant model (P = 8.88 x 10(-9), OR = 0.69, 95% CI: 0.61-0.79). In contrast to the Caucasian, this risk allele was the major allele in the Chinese Han; the risk allele frequency was higher in Chinese Han than in Caucasian. We did not find the association between this SNP and any subphenotype of SLE. The SNP rs2248932 was correlated to the expression of BLK mRNA. We conclude that the association of the BLK region with SLE was replicated in Chinese Han population living in mainland.

Keloids are common abnormal raised fibroproliferative lesions that can occur following even minor cutaneous trauma. There is strong evidence suggesting a genetic susceptibility in individuals affected by keloids including familial heritability, common occurrence in twins, and high prevalence in certain ethnic populations. Human leukocyte antigens (HLAs) have been proposed to modulate the immune response to keloids. HLA class II molecules are critical to the development of CD4(+) T-lymphocyte responses through their role in antigen presentation. No report has been published on HLA-DRB1 association with keloids in Chinese Han individuals. To investigate the etiology of keloids, the polymerase chain reaction sequence-specific primer method was used to analyze the distribution of HLA-DRB1 alleles in 192 patients with keloids and 273 healthy control individuals. Controls were matched by sex, age, and race. The HLA-DRB1*15 allele [19.01% vs 12.09%, odds ratio(OR) = 2.10, Pc = 0.024] was significantly more prevalent among keloid patients than healthy controls, whereas the frequency of the HLA-DRB1*03 allele (1.04% vs 4.95%, OR = 0.19, Pc = 0.022) was lower among keloid patients. Furthermore, through stratified analysis, we found that the HLA-DRB1*15 allele is related to the multiple-site group, severe group, and family history of keloids. This study supports an association between HLA-DRB1 alleles and susceptibility or resistance to keloids in Chinese Han individuals. The association of certain HLA alleles with susceptibility or resistance to keloids provides clues to choosing proper preventive strategies against keloid disease.

Systemic lupus erythematosus (SLE) is a complex systemic disease influenced by genetic and environmental factors. The exact pathogenesis of SLE is still unknown. Recently, several genome-wide association studies (GWA) in European population have found many novel susceptibility genes for SLE including TNFAIP3. In order to examine whether TNFAIP3 is associated with SLE in Chinese Han population, we genotyped one of its non-synonymous mutation SNP rs2230926, showing significant association evidence with SLE in European population, with 1,420 cases and 4,461 controls of Chinese Han by using Sequenom MassArray system. Highly significant association between SNP rs2230926 and SLE of Chinese Han was detected [OR = 1.65, 95% confidence interval (CI): 1.392-1.986, P = 2.03 x 10(-8)]. Interestingly, rs2230926 of TNFAIP3 was also associated with arthritis, ANA and some other subphenotypes of the disease. Our findings suggest that SNP rs2230926 in the TNFAIP3 might be a common genetic factor for SLE within different populations in terms of Chinese Han and European population.

Summary Background Some studies have suggested that human HLA status might potentiate development of keloids phenotype, and exists ethnic differences. No report has been published about HLA-DQA1 and DQB1 alleles associated with keloids in Chinese Hans. Objectives To investigate whether HLA-DQA1 and DQB1 alleles are associated with genetic susceptibility to keloids in Chinese Hans. Methods Polymerase chain reaction-sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA-DQA1 and DQB1 alleles among 192 patients with keloids and 273 healthy controls in Chinese Hans. Results (1) The frequencies of HLA-DQA1*0104, DQB1*0501 and DQB1*0503 (OR = 2.13, P c = 0.0063; OR = 14.42, P c −7 and OR = 6.09, P c −7 , respectively) were significantly higher, while the frequencies of DQA1*0501, DQB1*0201 and DQB1*0402 (OR = 0.46, P c = 0.0099; OR = 0.24, P c −4 and OR = 0.10, P c = 0.0054, respectively) were lower in patients than in controls. (2) In this study significant susceptibility haplotypes to keloids were DQA1*0104–DQB1*0501 and DQA1*0104–DQB1*0503. (3) HLA-DQB1*0501 and DQB1*0503 were positively associated with all subgroups of keloid patients. However, the DQA1*0104 (OR = 2.51, P c = 0.0009; OR = 2.22, P c = 0.0090 and OR = 2.20, P c = 0.0117, respectively) was only prevalent in keloid patients with single site, moderate severity and negative family history. (4) HLA-DQB1*0201 (OR = 0.27, P c = 0.0018 and OR = 0.27, P c = 0.0012, respectively) and DQB1*0402 (OR = 0.07, P c = 0.0270 and OR = 0.07, P c = 0.0306, respectively) were negatively associated with moderate severity and negative family history in keloids, moreover, HLA-DQB1*0201 (OR = 0.23, P c = 0.0003) and DQA1*0501 (OR = 0.43, P c = 0.0234) were less prevalent in patients with single site. Conclusion This study demonstrated the positive association of HLA-DQA1 and DQB1 alleles and haplotypes with keloids.