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New Locus ID'd for Infantile Hypertrophic Pyloric Stenosis
Inverse correlation seen for cholesterol-lowering alleles at nearby locus, risk of IHPS

WEDNESDAY, Aug. 21 (HealthDay News) -- A novel locus that is associated with infantile hypertrophic pyloric stenosis (IHPS) has been identified, according to a study published in the Aug. 21 issue of the Journal of the American Medical Association.

Bjarke Feenstra, Ph.D., from Statens Serum Institut in Copenhagen, Denmark, and colleagues used data from three independent sample sets to identify genetic association with IHPS. In stage 1, reference data were used from 1,001 Danish surgery-confirmed samples and 2,371 disease-free controls. The five most significant loci were tested in stage 2 in independent case-control sample sets from Denmark, Sweden, and the United States, with 1,663 cases and 2,315 controls.

The researchers identified a new genome-wide significant locus for IHPS at 11q23.3. The lowest P value at the locus was seen with the single nucleotide polymorphism (SNP) rs12721025 (odds ratio, 1.59). The locus was located 301 bases downstream of the apolipoprotein A-I gene, and was associated with SNPs linked to circulating cholesterol levels. The cholesterol lowering allele at these SNPs was consistently linked with elevated risk of IHPS.

"In conclusion, we identified a novel genetic locus that associates with IHPS at genome-wide significance," the authors write. "Characteristics of this locus suggest the possibility of an inverse relationship between levels of circulating cholesterol in neonates and IHPS risk. Further investigation is required to illuminate the functional significance of the association identified here."

Several authors disclosed being listed on the priority patent application on the use of genetic profiling to identify newborns at risk of IHPS.

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April 23, 2014

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