RESUMO
The objective of this study was to investigate the association between mRNA expression and single nucleotide polymorphisms (SNPs) of the ATP-binding cassette transporter (ABCA1) gene, apolipoprotein A1 (APOA1) gene, low-density lipoprotein (LDLR) gene and RNA gene located in the CDKN2B-CDKN2A cluster (CDKN2B-AS1) involved in lipid metabolism and the occurrence of intracranial aneurysm (IA). Fifty three IA patients, and 27 controls (IA-free) were enrolled in this study and were genotyped for seven single nucleotide polymorphisms. Increased expression of the LDLR gene in IA patients was observed. The A/G genotype and the A allele of the c. -113G>A polymorphism of the APOA1 gene were associated with increased occurrence of IA (ORs 12.36 and 14.14, respectively), while the G/G genotype and G allele showed the opposite tendency (ORs 0.06 and 0.07, respectively). We also detected that the A/A-G/A combined genotype of the c. -113G>A - APOA1 and g.46859A>G - LDLR SNPs was associated with a decreased occurrence of IA. Moreover, the A/G-G/G combined genotype of the c.656G>A - ABCA1 and c. -113G>A - APOA1 was associated with a decreased occurrence of IA. The results of our study suggest the association between expression and variability of lipid metabolism genes and occurrence of IA.
Assuntos
Regulação da Expressão Gênica , Variação Genética , Aneurisma Intracraniano/genética , Metabolismo dos Lipídeos/genética , Adulto , Alelos , Estudos de Casos e Controles , Demografia , Epistasia Genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
The product of the LIG3 gene encodes DNA ligase III, which is involved in the repair of oxidatively damaged DNA in the base excision repair pathway. We hypothesized that polymorphism in this gene may change susceptibility to oxidative stress and predispose individuals to the development of keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD). Therefore, we investigated the association between genotypes and haplotypes of the g.29661G>A polymorphism (rs1003918) and the g.29059C>T polymorphism (rs1052536) of the LIG3 gene and the occurrence of KC and FECD in patients with FECD (258 individuals) or KC (283) and ethnically matched controls (300). The A/A genotype and the A allele of the g.29661G>A polymorphism were associated with increased occurrence of KC, while the G allele of this polymorphism was positively correlated with a decreased occurrence of this disease. The T/C genotype of the g.29059C>T polymorphism was associated with decreased FECD occurrence. In addition, the AT haplotype was associated with increased occurrence of KC and FECD, while the GT haplotype was associated with decreased occurrence of these diseases. The g.29661G>A and g.29059C>T polymorphisms may play a role in the KC and FECD pathogenesis and can be considered as markers in these diseases.