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Publication
Repeat polymorphisms in the Homo sapiens heme oxygenase-1 gene in diabetic and
idiopathic gastroparesis.
Authors Gibbons SJ, Grover M, Choi KM, Wadhwa A, Zubair A, Wilson LA, Wu Y, Abell TL,
Hasler WL, Koch KL, McCallum RW, Nguyen LAB, Parkman HP, Sarosiek I, Snape WJ,
Tonascia J, Hamilton FA, Pasricha PJ, Farrugia G
Submitted By Submitted Externally on 4/9/2018
Status Published
Journal PLoS ONE
Year 2017
Date Published
Volume : Pages 12 : e0187772
PubMed Reference 29161307
Abstract Idiopathic and diabetic gastroparesis in Homo sapiens cause significant
morbidity. Etiology or risk factors have not been clearly identified. Failure to
sustain elevated heme oxygenase-1 (HO1) expression is associated with delayed
gastric emptying in diabetic mice and polymorphisms in the HO1 gene (HMOX1, NCBI
Gene ID:3162) are associated with worse outcomes in other diseases., Our
hypothesis was that longer polyGT alleles are more common in the HMOX1 genes of
individuals with gastroparesis than in controls without upper gastrointestinal
motility disorders., Repeat length was determined in genomic DNA. Controls with
diabetes (84 type 1, 84 type 2) and without diabetes (n = 170) were compared to
diabetic gastroparetics (99 type 1, 72 type 2) and idiopathic gastroparetics (n
= 234). Correlations of repeat lengths with clinical symptom sub-scores on the
gastroparesis cardinal symptom index (GCSI) were done. Statistical analyses of
short (<29), medium and long (>32) repeat alleles and differences in allele
length were used to test for associations with gastroparesis., The distribution
of allele lengths was different between groups (P = 0.016). Allele lengths were
longest in type 2 diabetics with gastroparesis (29.18±0.35, mean ± SEM) and
longer in gastroparetics compared to non-diabetic controls (28.50±0.14 vs
27.64±0.20 GT repeats/allele, P = 0.0008). Type 2 diabetic controls had longer
alleles than non-diabetic controls. In all gastroparetic groups, allele lengths
were longer in African Americans compared to other racial groups, differences in
the proportion of African Americans in the groups accounted for the differences
between gastroparetics and controls. Diabetic gastroparetics with 1 or 2 long
alleles had worse GCSI nausea sub-scores (3.30±0.23) as compared to those with 0
long alleles (2.66±0.12), P = 0.022., Longer poly-GT repeats in the HMOX1 gene
are more common in African Americans with gastroparesis. Nausea symptoms are
worse in subjects with longer alleles.




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