Premium
IL 10 low‐frequency variants in B ehçet's disease patients
Author(s) -
Matos Mafalda,
Xavier Joana M.,
Abrantes Patrícia,
Sousa Inês,
Rei Nádia,
Davatchi Fereydoun,
Shahram Farhad,
Jesus Gorete,
Barcelos Filipe,
Vedes Joana,
Salgado Manuel,
Abdollahi Bahar Sadeghi,
Nadji Abdolhadi,
MoraesFontes Maria Francisca,
Shafiee Niloofar Mojarad,
Ghaderibarmi Fahmida,
Vaz Patto José,
Crespo Jorge,
Oliveira Sofia A.
Publication year - 2017
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.12369
Subject(s) - sanger sequencing , genetics , gene , minor allele frequency , single nucleotide polymorphism , biology , coding region , promoter , allele , untranslated region , genetic association , intron , genome wide association study , allele frequency , genotype , microbiology and biotechnology , dna sequencing , gene expression , rna
Abstract Aim To explain the missing heritability after the genome‐wide association studies era, sequencing studies allow the identification of low‐frequency variants with a stronger effect on disease risk. Common variants in the interleukin 10 gene ( IL 10 ) have been consistently associated with Behçet's disease ( BD ) and the goal of this study is to investigate the role of low‐frequency IL 10 variants in BD susceptibility. Methods To identify IL 10 low‐frequency variants, a discovery group of 50 Portuguese BD patients were Sanger‐sequenced in a 7.7 kb genomic region encompassing the complete IL 10 gene, 0.9 kb upstream and 2 kb downstream, and two conserved regions in the putative promoter. To assess if the novel variants are BD ‐ and/or Portuguese‐specific, they were assayed in an additional group of BD patients (26 Portuguese and 964 Iranian) and controls (104 Portuguese and 823 Iranian). Results Rare IL 10 coding variants were not detected in BD patients, but we identified 28 known single nucleotide polymorphisms with minor allele frequencies ranging from 0.010 to 0.390, and five novel non‐coding variants in five heterozygous cases. ss836185595, located in the IL 10 3′ untranslated region, was also detected in one Iranian control individual and therefore is not specific to BD . The remaining novel IL 10 variants (ss836185596 and ss836185602 in intron 3, ss836185598 and ss836185604 in the putative promoter region) were not found in the replication dataset. Conclusion This study highlights the importance of screening the whole gene and regulatory regions when searching for novel variants associated with complex diseases, and the need to develop bioinformatics tools to predict the functional impact of non‐coding variants and statistical tests which incorporate these predictions.