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Study On Association Of Multiple Genes Interactions And Acne Risk

Posted on:2017-01-16Degree:DoctorType:Dissertation
Country:ChinaCandidate:H Y WangFull Text:PDF
GTID:1224330491458140Subject:Dermatology and Venereology
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Background Objective We evaluated the associations of SELL, MRPS36P2, TP63, DDB2, CACNA1 H, ADAM19, GNAI1, CDH13 and GABRG2 gene interaction on the incidence of acne, and determined the epistasis and combined effects of SELL, DDB2 and TP63 on risk for acne.Method In this study, 2916 acne cases and 4716 controls were divided into two types, and the correlation analysis was performed. The validation data were then combined with previous GWAS data to estimate the optimal association model for SELL, MRPS36P2, TP63, DDB2, CACNA1 H, ADAM19, GNAI1, CDH13 and GABRG2 gene variants, respectively. Logistic regression analysis was used to analyze the interaction of TP63, DDB2, and SELL genes, and to estimate the combined effects of SELL and DDB2, SELL and TP63, according to the best association model. Finally, we grouped the cases according to the joint effect, and compared the clinical features of the patients with acne with the above genetic risk variants and without the risk of mutation.Result(1)Analysis results related SELL, MRPS36P2, TP63, DDB2, CACNA1 H, ADAM19, GNAI1, CDH13 and GABRG2 gene in 2916 cases and 4716 controls prompt nine genes and the onset of acne were strong relationship;(2)Previous GWAS research data combined with analysis SELL, MRPS36P2, TP63, DDB2, CACNA1 H, ADAM19, GNAI1, CDH13 and GABRG2 association model nine variations that: SELL_rs7531806_A, DDB2_rs747650_G, MRPS36P2-rs7660345-T, GABRG2-rs10491327-A, GNAI1- rs1828522-G, CDH13-rs77502020-G, the best correlation model CACNA1H-rs2753325-a seven genes are dominant model(dominant model), and the best correlation model TP63_rs7631358_A, ADAM19_rs6896064_C two genes are cumulative model(additive model)(3)And generalized multifactor dimensionality reduction method to analyze the number of points we drop by multifactor dimensionality(MDR) gene- gene interaction Results: There was a significant interaction between the nine genes, including SELL × MRPS36P2(Padjusted = 4.15 × 10-10), TP63 × DDB2(Padjusted = 7.62 × 10-08), DDB2 × CACNA1H(Padjusted = 1.89 × 10-07), ADAM19 × GNAI1 × CDH13(Padjusted = 1.22 × 10-04) and ADAM19 × GABRG2 × GNAI1 × CDH13(Padjusted = 6.33 × 10-05).(4)We genome-wide association study based on previous severe acne basis(GWAS) studies to explore the relevance of these nine genes and Chinese Han acne phenotype.(5)We compared the clinical features between the carriers of the risk alleles and non-carriers acne patients, and observed obvious clinical difference between the two group.Conclusion This study demonstrates the interaction between these genes associated with the risk of acne in Chinese Han population of these genes- gene interaction prompted the different roles of these sites in the pathogenesis of acne. The findings not only deepen our understanding of genetic interactions acne understanding and awareness, and to explain the occurrence of additional risk factors for certain individuals’ acne. However, the interaction of these genes result needs to be confirmed in the future, other independent studies.
Keywords/Search Tags:Acne, Interaction, SELL, MRPS36P2, TP63, DDB2, CACNA1H, ADAM19, GNAI1, CDH13, GABRG2, Clinical feature
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