GSTP1 homozygous Val105/Val105 polymorphism is predominant in late vs early onset asthma.

BACKGROUND

Single nucleotide polymorphisms (SNPs) can contribute to the risk of developing asthma. The glutathione-S-transferase (GST) system detoxifies reactive oxygen species, increased in asthma. Detox ability declines over time and may contribute to asthma later in life. We set out to determine if polymorphisms of the GST enzymes GSTM1, GSTT1 and GSTP1 were related with the age of onset in asthma.

METHODS

293 patients with asthma underwent SNP analysis using polymerase chain reaction, restriction enzyme digestion and electrophoresis. Statistical analyses were done to integrate the presence of each variant with clinical characteristics. Bioinformatics analyses of human databases inferred GSTP1 expression and its biological role.

RESULTS

65.9% of patients presented GSTM1 deletion while 24.4% had deletion of GSTT1. In exon 5 of GSTP1 Ile105Val (A131G), 34% had Ile105/Ile105; 48.8% Ile105/Val105 and 17.1% Val105/Val105 genotypes. GSTP1 Val105/Val105 was statistically significantly enriched (P = 0.016) in patients with late- vs early-onset asthma. Late-onset asthma patients had statistically significant less atopy (P = 0.0465) and increased high FeNO frequency (P = 0.0106) than those with early onset asthma. GSTP1 was predominantly expressed in lung epithelium and gene co-expression analysis showed GSTP1 mapping to IL-4/IL-13 signalling. GSTP1 expression was positively correlated with that of IL13, IL4 and IL5 in a cohort of 99 patients with moderate-to-severe asthma from U-BIOPRED.

CONCLUSIONS

GSTP1 Val105/Val105 polymorphism is predominant in patients with late-onset asthma. We postulate that SNPs in GSTP1 may decrease the ability of airways epithelium to detox, in turn modulating IL-4 and IL-13 signalling.