Gene-gene interactions in IL23/Th17 pathway contribute to psoriasis susceptibility in Chinese Han population
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
Authors: Wang, W. -J.; Yin, X. -Y.; Zuo, X. -B.; Cheng, H.; Du, W. -D.; Zhang, F. -Y.; Yang, S.; Zhang, X. -J.
Abstract
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(chi(2) = 5.02(1), P = 0.025) and three pair-wise gene-gene interactions between IL12RB1 and CCR4(chi(2) = 11.66(4), P = 0.0201), IL22 and CCR4 (chi(2) = 11.97(4), P = 0.0176), IL12RB1 and IL6 (chi(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.
Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus
ANNALS OF THE RHEUMATIC DISEASES
Authors: Sanchez, Elena; Nadig, Ajay; Richardson, Bruce C.; Freedman, Barry I.; Kaufman, Kenneth M.; Kelly, Jennifer A.; Niewold, Timothy B.; Kamen, Diane L.; Gilkeson, Gary S.; Ziegler, Julie T.; Langefeld, Carl D.; Alarcon, Graciela S.; Edberg, Jeffrey C.; Ramsey-Goldman, Rosalind; Petri, Michelle; Brown, Elizabeth E.; Kimberly, Robert P.; Reveille, John D.; Vila, Luis M.; Merrill, Joan T.; Anaya, Juan-Manuel; James, Judith A.; Pons-Estel, Bernardo A.; Martin, Javier; Park, So-Yeon; Bang, So-Young; Bae, Sang-Cheol; Moser, Kathy L.; Vyse, Timothy J.; Criswell, Lindsey A.; Gaffney, Patrick M.; Tsao, Betty P.; Jacob, Chaim O.; Harley, John B.; Alarcon-Riquelme, Marta E.; Sawalha, Amr H.
Abstract
Objective Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus. Materials and methods 4001 European-derived, 1547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria. Results Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0 x 10(-6), OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p= 0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM and discoid rash (p= 0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p= 0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and haematological disorder (p= 0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these associations are significant with a false discovery rate of < 0.05 and pass the significance threshold using Bonferroni correction for multiple testing. Conclusion Significant associations were found between lupus clinical manifestations and the FCGR2A, ITGAM, STAT4, TNSF4 and IL21 genes. The findings suggest that genetic profiling might be a useful tool to predict disease manifestations in lupus patients in the future.
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