Multiple variants in 5q31.1 are associated with systemic lupus erythematosus susceptibility and subphenotypes in the Han Chinese population.

BACKGROUND: A previous study provided evidence for a genetic association between PPP2CA on 5q31.1 and systemic lupus erythematosus (SLE) across multi-ancestral cohorts, but failed to find significant evidence for an association in the Han Chinese population. OBJECTIVES: To explore the association between this locus and SLE using data from our previously published genome-wide association study (GWAS). METHODS: Single-nucleotide polymorphisms (SNPs) rs7726414 and rs244689 (near TCF7 and PPP2CA in 5q31.1) were selected as candidate independent associations from a large-scale study in a Han Chinese population consisting of 1047 cases and 1205 controls. Subsequently, 3509 cases and 8246 controls were genotyped in two further replication studies. We then investigated the SNPs' associations with SLE subphenotypes and gene expression in peripheral blood mononuclear cells. RESULTS: Highly significant associations with SLE in the Han Chinese population were detected for SNPs rs7726414 and rs244689 by combining the genotype data from our previous GWAS and two independent replication cohorts. Further conditional analyses indicated that these two SNPs contribute to disease susceptibility independently. A significant association with SLE, age at diagnosis < 20 years, was found for rs7726414 (P = 0·001). The expression levels of TCF7 and PPP2CA messenger RNA in patients with SLE were significantly decreased compared with those in healthy controls. CONCLUSIONS: This study found evidence for multiple associations with SLE in 5q31.1 at genome-wide levels of significance for the first time in a Han Chinese population, in a combined genotype dataset. These findings suggest that variants in the 5q31.1 locus not only provide novel insights into the genetic architecture of SLE, but also contribute to the complex subphenotypes of SLE.

Genetic variants of the genes encoding zinc finger protein 313 and interleukin-13 confer a risk for psoriasis in a Chinese Uygur population.

BACKGROUND: Recent work using genome­wide association studies (GWAS) in Chinese Han and white populations have discovered several novel psoriasis susceptibility genes. AIM: To examine whether the risk loci for psoriasis identified in previous GWAS in a white population are also associated with psoriasis in a Chinese Uygur population in Xinjiang. METHODS: Genotyping analysis of eight single-nucleotide polymorphisms (SNPs) associated with psoriasis was performed for 539 patients with psoriasis and 749 controls, all of Chinese Uygur descent, using a commercial assay. RESULTS: Two SNPs had an association with psoriasis in this Chinese Uygur population: SNP rs495337 in the gene encoding for zinc finger protein 313 (P < 0.001; OR = 0.80) and SNP rs20541 of the gene encoding for interleukin-13 (P < 0.001; OR = 0.82). In subgroup analyses, the two SNPs were significantly associated (P < 0.05) with type I psoriasis, Rs495337 showed statistically difference between positive family history of psoriasis patients and controls whereas rs20541 might preferentially associated with negative family history psoriasis patients. Interestingly, using multifactor dimensionality reduction, a significant two-locus interaction was seen between rs495337 and rs20541, with a crossvalidation consistency of 4/5 and average balanced prediction (accuracy 55.5%, P < 0.001). CONCLUSIONS: ZNF313 and IL-13 are associated with risk for psoriasis in a Chinese Uygur population, and there is an effect of interaction between the two genes on this risk.

Gene-gene interactions in IL23/Th17 pathway contribute to psoriasis susceptibility in Chinese Han population.

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease. IL23/Th17 is a newly confirmed pathway in psoriasis. OBJECTIVE: To investigate the gene-gene interactions in IL23/Th17 pathway underlying psoriasis. METHODS: A total of 299 single-nucleotide polymorphisms from 11 genes in IL23/Th17 pathway were genotyped on 1139 patients with psoriasis and 1694 controls. Multifactor dimensionality reduction and logistic regression algorithms were applied to explore the gene-gene interactions. RESULTS: We found that there were a three-way interaction among IL21, CCR4 and TNF(χ(2) = 5.02(1), P = 0.025) and three pair-wise gene-gene interactions between IL12RB1 and CCR4(χ(2) = 11.66(4), P = 0.0201), IL22 and CCR4 (χ(2) = 11.97(4), P = 0.0176), IL12RB1 and IL6 (χ(2) = 7.31(1), P = 0.0069) in psoriasis. CONCLUSIONS: Our results might be helpful for explaining the missing heritability of the psoriasis due to epistasis and provide a deep insight into the important role of the IL23/Th17 pathway in the pathogenesis of psoriasis.

A single-nucleotide polymorphism rs4639966 in 11q23.3 is associated with clinical features of systemic lupus erythematosus in the Chinese population.

In our previous genome-wide association study (GWAS), we identified an association signal of the single-nucleotide polymorphism (SNP) rs4639966 (p = 1.25 × 10(-16), odds ratio [OR] = 1.29) within 11q23.3. The aim of this study was to investigate its relationship with disease subphenotypes, including renal nephritis, photosensitivity, antinuclear antibody (ANA), age at diagnosis, malar rash, discoid rash, immunological disorder, oral ulcer, hematological disorder, neurological disorder, serositis, arthritis and vasculitis. In this study, we used 4199 cases and 8255 controls from our previous GWAS to explore the association between 11q23.3 with subphenotypes of systemic lupus erythematosus (SLE). Data were analyzed with PLINK 1.07 software. Significant associations were found for the SNP rs4639966 of 11q23.3 with SLE of age at diagnosis <20 years (OR = 1.18, p = 0.0049), malar rash (OR = 1.13, p = 0.01) and vasculitis (OR = 1.17, p = 0.02). The study suggested that 11q23.3 might not only play important roles in the development of SLE, but also contribute to the complex phenotypes of SLE.

Genetic variant rs4982958 at 14q11.2 is associated with allergic rhinitis in a Chinese Han population running title: 14q11.2 is a susceptibility locus for allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is one of the most common diseases caused by the combined effects of intrinsic factors (susceptibility genes and immunological status) and the external environment. Analyses of ascendant family history of atopic disease suggest that AR and atopic dermatitis might share a similar genetic background. OBJECTIVE: To conduct a case-control study in a Chinese Han population to evaluate the potential influence of single nucleotide polymorphisms (SNPs) at FLG, 5q22.1, 11q13.5, 14q11.2 and 20q13.33 on AR. METHODS: Ten SNPs--rs11204971 and rs3126085 at FLG, rs10067777, rs7701890, rs13360927, and rs13361382 at 5q22.1, rs6010620 at 20q13.33, rs7936562 and rs7124842 at 11q13.5, and rs4982958 at 14q11.2 were genotyped in 363 cases and 668 controls using the Sequenom MassArray system. Data were analyzed with PLINK 1.07 software. RESULTS: The T allele of rs4982958 at 14q11.2 was observed to be significantly associated with AR (P = .002, OR = 0.73, P(Bonferront) = .02). Genotype-based association testing revealed that the recessive model might provide the best fit for rs4982958 (P(Bonferroni) = .01). In subphenotype analyses, the rs4982958 T allele was also significantly associated with persistent AR (P = .01) and more than 2 positive skin prick tests (P = .038). CONCLUSION: We identified a novel susceptibility locus 14q11.2 for AR that might bear candidate genes conferring susceptibility to AR and affecting disease phenotypes.

Comparisons of clinical features of HLA-DRB1*07 positive and negative vitiligo patients in Chinese Han population.

BACKGROUND: Human leucocyte antigen (HLA)-II alleles have been found to be associated with vitiligo in different populations, and several studies also suggested that HLA class II alleles/haplotypes were associated with a different type vitiligo. Of HLA class II alleles, DRB1*07 has consistently shown a positive association with vitiligo in Chinese Han population. OBJECTIVE: To further explore the relationship between DRB1*07 and vitiligo and to evaluate the DRB1*07 effect on the clinical features of vitiligo in Chinese Han population. METHODS: This study investigated DRB1*07 allele distribution in 1178 unrelated Chinese vitiligo patients and 1743 healthy controls using polymerase chain reaction/sequence specific primer method and observed clinical differences between DRB1*07 positive and DRB1*07 negative patients. RESULTS: The analysis of the 1178 cases and 1743 controls revealed a highly association between DRB1*07 allele and vitiligo [odds ratio (OR) = 1.97, P = 2.13 × 10(-17) ]. DRB1*07 positive patients had early disease onset (OR = 1.49, P = 0.001), higher frequency of family history (OR = 1.44, P = 0.006) compared with DRB1*07 negative patients. CONCLUSIONS: The DRB1*07 showed significant association with vitiligo in the study population. This study confirmed that DRB1*07 positive patients had some obvious clinical differences from DRB1*07 negative patients in the Chinese Han population.

The effect of overweight and obesity on psoriasis patients in Chinese Han population: a hospital-based study.

BACKGROUND: Accumulating evidence indicates that psoriasis is associated with increased risk of overweight and obesity. However, few studies have investigated this relationship in Chinese Han population. OBJECTIVE: The aim of this study was to explore the relationship between overweight/obesity and psoriasis and to evaluate the overweight/obesity effect on the clinical features of psoriasis in Chinese Han population. METHODS: A hospital-based study was conducted, which involved in 4452 patients and 1166 controls of Chinese Han through epidemiological investigation. Controls used in the study were individuals without psoriasis from health examination centre, and other skin disease patients from outpatient department. RESULTS: Compared with the control group, a significantly greater prevalence of overweight and obesity was observed in psoriasis patients. The estimated ORs were 1.301 (95% CI, 1.105-1.531) and 1.680 (95% CI, 1.134-2.491) respectively. The disease severity of psoriasis measured by psoriasis area and severity index (PASI) was statistically correlated with body mass index (BMI) (r = 0.184, P < 0.01). Moreover, a high proportion of overweight patients had affected hands or/and feet, buttocks, trunk, legs, arms and arthritis (P < 0.01). CONCLUSIONS: Our study suggested that psoriatic patients have a higher prevalence of overweight and obesity compared with non-psoriatic patients in Chinese Han population. Overweight and obesity has different risk effect on severity and manifestations of psoriasis and might be useful for better evaluating psoriasis clinically.

Association of HLA-DRB1 alleles with keloids in Chinese Han individuals.

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.

TNIP1, SLC15A4, ETS1, RasGRP3 and IKZF1 are associated with clinical features of systemic lupus erythematosus in a Chinese Han population.

Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous clinical manifestations influenced by genetic and environmental factors. Five novel susceptibility genes (TNIP1, SLC15A4, ETS1, RasGRP3 and IKZF1) for SLE have been identified in a recent genome-wide association study of a Chinese Han population. This study investigated their relationships with disease subphenotypes, including renal nephritis, photosensitivity, antinuclear antibody (ANA), age at diagnosis, malar rash, discoid rash, immunological disorder, oral ulcer, hematological disorder, neurological disorder, serositis, arthritis and vasculitis. Significant associations were found for the single nucleotide polymorphism rs10036748 of TNIP1 with photosensitivity (odds ratio (OR) = 0.87, p = 0.01) and vasculitis (OR = 1.18, p = 0.04); rs10847697 of SLC15A4 with discoid rash (OR = 1.18, p = 0.02); rs6590330 of ETS1 with SLE of age at diagnosis <20 years (OR = 1.24, p = 8.91 x 10(-5)); rs13385731 of RasGRP3 with malar rash (OR = 1.20, p = 0.01), discoid rash (OR = 0.78, p = 0.02) and ANA (OR = 0.72, p = 0.004); rs4917014 of IKZF1 with renal nephritis (OR = 1.13, p = 0.02) and malar rash (OR = 0.83, p = 0.00038), respectively. The study suggested that these susceptibility genes might not only play important roles in the development of SLE, but also contribute to the complex phenotypes of SLE.