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Novel SNPs identified for bone mineral accretion in children
Two novel tubulin pathway single nucleotide polymorphisms were associated with independent interactive effects of cumulative corticosteroid dose on bone mineral accretion in children with asthma who underwent various oral prednisone bursts, according to study results.
Significant decreases in bone mineral accretion occur with long-term intermittent oral corticosteroid use in children with asthma. Heung-Woo Park, MD, PhD, of the Channing Division of Network Medicine and the division of pulmonary and critical care medicine at Brigham and Women’s Hospital and Harvard Medical School, and colleagues sought to identify possible genetic factors that influence oral corticosteroid dose effects on bone mineral accretion in children with asthma.
The researchers conducted a gene-by-oral corticosteroid interaction genome-wide association study of bone mineral accretion in 489 white patients included in the Childhood Asthma Management Program trial. All patients used short-term oral prednisone bursts for acute asthma exacerbations.
According to study results, two (rs9896933 and rs2074439) of the 2,000 SNPs included in the genome-wide association study were associated with decreased bone mineral accretion and the tubulin gamma pathway.
The rs9896933 variant, located on the intron of tubulin folding cofactor D gene, met the criteria for genome-wide significance (P=3.15 x 10–⁸) and the rs2074439 variant (P=2.74 x 10–⁴) indicated significant cis-regulatory effects on dexamethasone-induced tubulin gamma gene expression in osteoblasts (P=8.64 x 10–⁴), according to the researchers.
“Interestingly, we found that bone mineral accretion worsened with increasing prednisone dose as the number of mutant alleles of the two SNPs increased,” the researchers wrote.
Disclosure: The researchers report receiving research support and consultancy fees from AstraZeneca, GlaxoSmithKline, Merck, the NIH, the NHLBI and Novartis.