GLCCI1 SNP Lowers Response to Inhaled Steroids in Asthma

rs37973 single neucleotide polymorphism tied to decreased inhaled glucocorticoid response

MONDAY, Sept. 26 (HealthDay News) -- Expression of a single nucleotide polymorphism (SNP) at rs37973 correlates with decreased glucocorticoid-induced transcript 1 gene (GLCCI1) expression, which is associated with a reduced response to inhaled glucocorticoids in patients with asthma, according to a study published online Sept. 26 in the New England Journal of Medicine to coincide with late-breaking presentations at the European Respiratory Society Congress, held from Sept. 24 to 28 in Amsterdam, Netherlands.

Kelan G. Tantisira, M.D., from the Channing Laboratory in Boston, and colleagues investigated whether pharmacogenetic variants are associated with the response to inhaled glucocorticoids in asthma. Using a family-based screening algorithm, statistically powerful variants were identified and analyzed from among 534,290 SNPs. Functional effects of the associations were characterized.

The investigators identified a significant association at SNP rs37972, which maps to the GLCCI1 and correlated perfectly with rs37973. This association was replicated in 935 individuals across four populations. Both rs37972 and rs37973 correlated with decreased GLCCI1 expression, and rs37973 was associated with lowered luciferase reporter activity in isolated cell systems. Pooled treatment trial analysis showed reduced lung function in response to inhaled glucocorticoids in individuals with the variant allele. Treated subjects who were homozygous for the mutant allele showed a mean increase in forced expiratory volume in one second which was only one third of the level of those who were homozygous for the wild-type allele (3.2±1.6 versus 9.4±1.1 percent). They also had a significantly higher risk of a poor response with genotype accounting for approximately 6.6 percent of overall inhaled glucocorticoid response variability.

"A functional GLCCI1 variant is associated with substantial decrements in the response to inhaled glucocorticoids in patients with asthma," the authors write.

One of the trials in the study was partially supported by GlaxoSmithKline, and genotyping services were provided by Affymetrix.

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