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International consensus statement on rhinosinusitis

TABLE IX-19 CRS-associated genes reported in more than one study. Genes are grouped according to putative biological role: a. Immune system-related, b. Epithelial barrier related, c. Difficult to categorize Gene Reference Immune System ALOX5AP Al-Shemari; 970 Henmyr 971 AOAH Bossé; 972 Zhang 973 IL1A Karjalainen; 974 Erbek; 975 Mfuna 976 IL1B Erbek; 975 Bernstein 977 IL10 Kim; 978 Bernstein; 977 Zhang 979 IL22RA1 Endam; 980 Henmyr 971 IL33 Buysschaert; 981 Kristjansson 982 IRAK-4 Tewfik; 983 Zhang 984 NOS1 Castano; 985 Zhang; 973 Henmyr 971 NOS1AP Zhang; 973 Henmyr 971 TAS2R38 Adappa; 611 Mfuna Endam; 964 Purnell 963 TGFB1 Kim; 986 Henmyr 971 TNFA Erbek; 975 Bernstein; 977 Batikhan 987 Barrier and Structural None None Not Easily Categorized DCBLD2 Pasaje; 988 Henmyr 971 PARS2 Bossé; 972 Henmyr 971 RYBP Bossé; 972 Zhang; 973 Cormier 958 Published genetic association studies in CRS have increased in number over the past decade, increasing the number of potential gene candidates (Table IX-19) and repeatedly implicating certain genes, supporting their rele vance to the disease process (Table IX-20). Gene candidates are categorized by location and function, grouped loosely into regulation of immune function, barrier function, and a broad category of SNPs in which effect on CRS pathophys iology is not yet known. Note that the high percentages of identified genes related to immune function may reflect a selection bias of candidate genes studied rather than their actual level of implication. These findings improve our understanding of the dis ease process and open potential new targets for therapy. In an example of this from Desrosiers et al., “hypothesis free” association studies suggested candidate genes asso ciated with epithelial and basement membrane structure and function. This led to exploration of barrier function in CRS patients, culminating in the recent identification of a defect in tissue repair and regeneration as an unexpected feature of CRS, 962 opening up the possibility of new drug treatments such as rho-kinase (ROCK) inhibitors to pro mote repair and regeneration.

TABLE IX-20 CRS-associated genes reported in a single study. Genes are grouped according to putative biological role: a. Immune system-related, b. Epithelial barrier related, c. Difficult to categorize Gene Reference Immune System ALOX15 Kristjansson 982 ALOX5 Al-Shemari 970 BDKRB2 Cormier 958 CD58 Pasaje 989 CD8A Alromaih 990 CIITA Bae 991 CNTN5 Cormier 958 COX2 Sitarek 992 CYSLTR1 (X) * Al-Shemari 970 FOXP1 Kristjansson 982 HLA-DQA1 Kristjansson 982 HLA-DQB1 Schubert 993 HLA-DRA Bohman 994 IGFBP7 Cormier 958 IL1RL1 Castano 985 IL1RN Cheng 995 IL18R1 Kristjansson 982 IL4 Zhang 979 MET Sitarek 992 MET1 Castano 985 OSF-2 (POSTN) Zielinska-Blizniewska 996 PDGFD Cormier 958 PRKCH Cormier 958 RAC1 Cormier 958 C SERPINA1 Kilty 997 TAS2R19 Purnell 963 TNFAIP3 Cormier 998 TP73 Tournas 999 TSLP Kristjansson 982 VSIR Bohman 994 Barrier and Structural BICD2 Bohman 994 CACNA1I Bossé 972 CACNA2D1 Cormier 958 CACNG6 Lee 1000 CDH23 Cormier 958 K6IRS2 Cormier 958 KCNAM1 Purkey 1001 KCNQ5 Purkey 1001 K6IRS4 Cormier 958 LAMA2 Bossé 972 LAMB1 Bossé 972 (Continues)