Novel polymorphisms in the promoter region of the perforin gene among distinct Brazilian populations and their functional impact
| Autor: | L. D. de Figueiredo Nicolete, Simone Kashima, Evandra Strazza Rodrigues, Tathiane M. Malta, Dimas Tadeu Covas, Helio Moraes-Souza, Rodrigo Haddad, Fernanda Bernadelli Garcia, Israel Tojal da Silva |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Pore Forming Cytotoxic Proteins
Immunology Molecular Sequence Data Black People Gene Expression Functional impact Single-nucleotide polymorphism Polymorphism Single Nucleotide White People Asian People Gene Frequency Genetics Cytotoxic T cell Humans Allele Promoter Regions Genetic Molecular Biology Gene Genetics (clinical) Alleles biology Base Sequence Perforin Haplotype Promoter General Medicine Molecular biology Killer Cells Natural Genetics Population Haplotypes biology.protein Brazil T-Lymphocytes Cytotoxic |
| Zdroj: | International journal of immunogenetics. 41(3) |
| ISSN: | 1744-313X |
| Popis: | Summary Cytotoxic T lymphocytes and natural killer cells play a crucial role in eliminating tumour and virus-infected cells. The perforin is a key part of the arsenal that these cells use to destroy their targets. In this study, we characterized single-nucleotide polymorphisms (SNPs) located in the promoter region of the perforin gene among distinct Brazilian ethnic groups. The study was carried out by sequencing this region in three groups: European, African and Asian descents. We demonstrated for the first time the occurrence of three new polymorphisms in the promoter region of gene PRF1: 494A/G (rs78058707), 720G/A (rs75925789) and 1176C/T (rs75183511). Three other SNPs already described in the literature 63A/G (rs35401316), 112A/G (rs10999428) and 1012C/T (rs35069510) were also detected. The SNPs are distributed differently in the ethnic groups studied. The 112G allele was observed at high frequency, especially among Asian descents (48.1%). The 1012T allele was detected only among European descents, the 494G allele only among Asian descents and 1176T allele only in African descents. Based on the association between the polymorphisms described, ten new haplotypes were originated. In functional analysis, we noticed that SNPs present in most common haplotypes cannot induce significant differences in expression levels of perforin alone. In conclusion, this study demonstrates for the first time the existence of three new polymorphisms in perforin promoter and, contrary to what was stated, the presence of these SNPs does not alter the levels of protein expression. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text