Yan-Yan Wu1, Jian-Ping Tang2, Qiang Liu3, Xiao-Dong Zheng1, Ling Fang1, Xian-Yong Yin1, Xiao-Yun Jiang1, Fu-Sheng Zhou1, Fei Zhu4, Bo Liang1, Yang Li1, Xian-Bo Zuo5, Xue-Jun Zhang1, Feng-Li Xiao6. 1. Institute of Dermatology and Department of Dermatology of First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China; State key Laboratory Incubation Base of Dermatology, Anhui Medical University, Hefei, Anhui, China. 2. Department of dermatology, Hunan Children' Hospital, Changsha, Hunan, China. 3. Department of dermatology, Shanxi Children' Hospital, Taiyuan, Shanxi, China. 4. Department of Plastic Surgery, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China. 5. Institute of Dermatology and Department of Dermatology of First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China; State key Laboratory Incubation Base of Dermatology, Anhui Medical University, Hefei, Anhui, China. Electronic address: zuoxianbo@ahmu.edu.cn. 6. Institute of Dermatology and Department of Dermatology of First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China; State key Laboratory Incubation Base of Dermatology, Anhui Medical University, Hefei, Anhui, China. Electronic address: xiaofengli@ahmu.edu.cn.
Abstract
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<0.005). The rs11357450 (Pcombined=7.79E-04, OR=1.39, logBayes Factor=1.29) deletion located in TMEM232 was identified to be the strongest variant. Analysis of the genetic model revealed that the dominant model best described rs11357450 (P=1.96E-03, OR=1.22; 95% CI=1.07-1.37). IHC showed that the expression of TMEM232 decreased gradually from the granular layer to the basal layer in AD, but in normal tissues, this trend was reversed. Additionally, positive cytoplasm staining was found in lymphocytes around the blood vessels in AD. CONCLUSIONS: The study indicates that TMEM232 in the 5q22.1 region is the causal gene for AD in the Chinese Han population.
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 ADpatients 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<0.005). The rs11357450 (Pcombined=7.79E-04, OR=1.39, logBayes Factor=1.29) deletion located in TMEM232 was identified to be the strongest variant. Analysis of the genetic model revealed that the dominant model best described rs11357450 (P=1.96E-03, OR=1.22; 95% CI=1.07-1.37). IHC showed that the expression of TMEM232 decreased gradually from the granular layer to the basal layer in AD, but in normal tissues, this trend was reversed. Additionally, positive cytoplasm staining was found in lymphocytes around the blood vessels in AD. CONCLUSIONS: The study indicates that TMEM232 in the 5q22.1 region is the causal gene for AD in the Chinese Han population.
Authors: Jeong Hyun Kim; So Yeon Lee; Mi Jin Kang; Jisun Yoon; Sungsu Jung; Hyun Ju Cho; Hyo Bin Kim; Soo Jong Hong Journal: Allergy Asthma Immunol Res Date: 2018-07 Impact factor: 5.764