62ª Reunião Anual da SBPC

C. Ciências Biológicas - 9. Imunologia - 3. Imunogenética

GENOTYPE AND ALLELE FREQUENCIES OF IL-18 GENE PROMOTER AND HLA-G GENE POLYMORPHISMS IN BRAZILIAN POPULATION FROM NORTHEAST REGION

Wenna Gleyce Araújo do Nascimento 1 Carolina Elisabeth Silva Xavier 2 Renata Gomes Alves 3 Neifi Hassan Saloum Deghaide 1 Eduardo Antônio Donadi 4 Janaína Cristiana de Oliveira Crispim 1

1. Department of Clinical abd Toxicological Analysis - UFRN 2. Programa de Pós-Graduação em Ciências Farmacêuticas - UFRN 3. Histocompatibility Laboratory, Serviço de Hemoterapia LTDA - HEMOVIDA 4. Faculty of Medicine of Ribeirão Preto, University of São Paulo - USP

INTRODUÇÃO:

Interleukin-18 (IL-18) is an inflammation-related cytokine that plays a central role both in innate defense reactions and in Th1 activation and specific immune responses. In addition to these effects, among its many activities IL-18 can stimulate production of inflammatory cytokines such as IFN-γ, TNF-α and IL-1β. Thus, it is perhaps not surprising that IL-18 was found to be associated with or demonstrated to contribute to numerous inflammatory-associated disorders. The genetic polymorphisms of IL-18 might be clinically important in the development and progression of diseases. For other hand, the HLA-G gene is predominantly expressed at the maternal-fetal interface. It's has been associated with tolerance and in the inhibition of the cytotoxic activity of Natural Killer (NK)- and CD8 T-cells. At least two variations in the 3'-untranslated region (3'-UTR) of HLA-G locus are associated with HLA-G expression levels. Thus, the aim of this study was to determine genotype and allele frequencies of IL-18 gene promoter and HLA-G gene polymorphisms in population from the Brazilian northeast-region.

METODOLOGIA:

A total of 212 healthy donors from different places in the state of Rio Grande do Norte, north-eastern Brazil, were recruited and the genomic DNA was extracted from peripheral blood using a salting-out procedure. Single nucleotide polymorphisms (SNPs) at positions -607 (C/A) and -137 (G/C), and 14-bp insertion/deletion polymorphism were analyzed by allele-specific polymerase chain reaction in 212 healthy Brazilian population.

RESULTADOS:

To our knowledge, the present study is the first to examine the -137G/C and -607C/A polymorphisms of the IL-18 gene and fourteen-base pair deletion/insertion polymorphism in healthy Brazilian population. The frequencies of the GG, GC, and CC genotypes of -137G/C were 53.80%, 39.13%, and 7.06% respectively. The frequencies of the CC, CA, and AA genotypes of -607C/A were 44.66%, 48.54% and 6.80% respectively, the frequencies of the -137G, -137C and -607C, -607A alleles among the healthy population were 0.734, 0.266 and 0.689, 0.311 respectively. In the current study, the 14-bp polymorphism was 32.23%, 48.19% and 19.58% for DD, DI and II genotypes. Analysis by polymerase chain reaction (PCR) showed that subjects homozygous for haplotype (-137G/-607 C) had higher levels of IL-18 and mRNA compared to other haplotypes, in addition, HLA-G alleles containing the 14-bp insertion are associated with decreased HLA-G mRNA levels, both can be related to pathological conditions.

CONCLUSÃO:

This work describes for the first time a genotype and allele frequencies promoter SNPs associated with IL-18 expression in Brazilian healthy individuals. However, the HLA-G 14-bp insertion/deletion polymorphism was analyzed as previously described in south-eastern Brazilian population, thus our data may contribute to elucidate the geographic distribution and population dynamics of the HLA-G genotype frequencies and to further explore the role of natural selection over the HLA-G gene in Brazil.

Palavras-chave: IL-18, HLA-G, Polymorphisms.