TY - JOUR
T1 - Analysis of Keratin Polypeptides 8 and 19 Variants in Inflammatory Bowel Disease
AU - Tao, Guo Zhong
AU - Strnad, Pavel
AU - Zhou, Qin
AU - Kamal, Ahmad
AU - Zhang, Leilei
AU - Madani, Nahid D.
AU - Kugathasan, Subra
AU - Brant, Steven R.
AU - Cho, Judy H.
AU - Omary, M. Bishr
AU - Duerr, Richard H.
PY - 2007/7
Y1 - 2007/7
N2 - Background/Aims: Keratin-8 (KRT8)-null mice develop spontaneous colitis and predisposition to liver injury. Human studies show that some KRT8 variants predispose to end-stage liver disease and progression and suggest that such variants might associate with UC or CD. We asked whether mutations in KRT8 or KRT19, the major intestinal keratins, are associated with UC/CD. Methods: Exonic regions of the KRT8/KRT19 genes were polymerase chain reaction-amplified using genomic DNA from 2 independent groups. Group I included 91 unrelated patients with CD, 93 unrelated patients with UC, and 70 unrelated/unaffected volunteers. KRT8 variants were also tested with pyrosequencing in Group II that included 682 independent nuclear families with both parents and at least 1 CD/UC-affected offspring and 273 unaffected controls. Both cohorts were enriched for familial IBD. Results: In Group I, KRT19 variants were identified in CD/UC patients within the promoter and exons 1+2, with similar mutation frequencies in the control/CD/UC groups. In contrast, 16 of 184 CD+UC patients harbored KRT8 heterozygous variants involving Gly62-to-Cys and Arg341-to-His and a novel Arg341-to-Cys, which were noted in 4 volunteers (Arg341-to-His) and correlated with extensive UC (P = .005). One family with unaffected parents had 3 pediatric-affected siblings with severe disease, 2 of whom are compound heterozygous (Gly62-to-Cys/Arg341-to-His). However, there was no significant departure from random transmission of the 3 alleles in Group II IBD families. Conclusions: KRT8 and KRT19 variants are not overtransmitted or associated with familial IBD, although a potential role in sporadic IBD cannot be excluded. A novel but rare keratin-8 Arg341-to-Cys is identified in IBD patients.
AB - Background/Aims: Keratin-8 (KRT8)-null mice develop spontaneous colitis and predisposition to liver injury. Human studies show that some KRT8 variants predispose to end-stage liver disease and progression and suggest that such variants might associate with UC or CD. We asked whether mutations in KRT8 or KRT19, the major intestinal keratins, are associated with UC/CD. Methods: Exonic regions of the KRT8/KRT19 genes were polymerase chain reaction-amplified using genomic DNA from 2 independent groups. Group I included 91 unrelated patients with CD, 93 unrelated patients with UC, and 70 unrelated/unaffected volunteers. KRT8 variants were also tested with pyrosequencing in Group II that included 682 independent nuclear families with both parents and at least 1 CD/UC-affected offspring and 273 unaffected controls. Both cohorts were enriched for familial IBD. Results: In Group I, KRT19 variants were identified in CD/UC patients within the promoter and exons 1+2, with similar mutation frequencies in the control/CD/UC groups. In contrast, 16 of 184 CD+UC patients harbored KRT8 heterozygous variants involving Gly62-to-Cys and Arg341-to-His and a novel Arg341-to-Cys, which were noted in 4 volunteers (Arg341-to-His) and correlated with extensive UC (P = .005). One family with unaffected parents had 3 pediatric-affected siblings with severe disease, 2 of whom are compound heterozygous (Gly62-to-Cys/Arg341-to-His). However, there was no significant departure from random transmission of the 3 alleles in Group II IBD families. Conclusions: KRT8 and KRT19 variants are not overtransmitted or associated with familial IBD, although a potential role in sporadic IBD cannot be excluded. A novel but rare keratin-8 Arg341-to-Cys is identified in IBD patients.
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U2 - 10.1016/j.cgh.2007.02.017
DO - 10.1016/j.cgh.2007.02.017
M3 - Article
C2 - 17509943
AN - SCOPUS:34447256176
SN - 1542-3565
VL - 5
SP - 857
EP - 864
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 7
ER -