Biomedical subjects

P McGrogan

Publications and source records attributed to P McGrogan.

4 recordsLinked to original sources

PubMed2006

Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease.

BACKGROUND AND AIMS: The OCTN1 (SLC22A4 1672C-->T) and OCTN2 (SLC22A5 -207G-->C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn's disease (CD), but their contribution in children has not been examined. METHODS: These OCTN1/2 variants and IBD5 marker single nucleotide polymorphisms (SNPs) (IGR2096a_1, IGR2198a_1, and IGR2230a_1) were examined in 299 Scottish children (200 with CD, 74 with ulcerative colitis (UC), and 25 with indeterminate colitis (IC)), together with 502 parents (for transmission disequilibrium testing) and 256 controls. RESULTS: All SNPs were in strong linkage disequilibrium (D' >0.94). TDT analysis showed association of the OCTN1 variant with inflammatory bowel disease (IBD) (p = 0.01) and CD (p = 0.04). Allele frequencies of the OCTN1/2 variants were significantly higher in IBD/CD cases (p<0.04). The homozygous mutant OCTN1/2 haplotype was increased in IBD (24.3% v 16.1%, p = 0.02) and UC (28.2% v 16.1%, p = 0.02) compared with controls. The OCTN1/2 variants were not independent of the background IBD5 risk haplotype in conferring disease susceptibility. Unifactorial analysis in CD patients showed that carriage of the TC haplotype was associated with lower weight, height, and BMI centile (<9(th) centile) at diagnosis (weight: 87.9% v 67.3% (p = 0.002), odds ratio (OR) = 3.52 (95% confidence interval, 1.51 to 8.22); height: 84.1% v 68.4% (p<0.05), OR = 2.44 (1.00 to 5.99); BMI: 79.6% v 61.1% (p = 0.02), OR = 2.49 (1.14 to 5.44)), and lower weight centile at follow up (87.5% v 64.6% (p = 0.03), OR = 3.83 (1.03 to 14.24)). Multifactorial binary logistic regression analysis confirmed association of the TC haplotype with lower weight centile at diagnosis (p = 0.02, OR = 3.41 (1.20 to 9.66)). CONCLUSIONS: These data implicate variants within the IBD5 haplotype, as determinants of disease susceptibility and growth indices in early onset IBD. The OCTN1/2 variants remain potential positional candidate genes, but require further analysis.

Adolescent↗

PubMed2006

The role of pro-inflammatory cytokines in inflammatory bowel disease growth retardation.

Childhood inflammatory bowel disease (IBD) especially those with Crohn disease is commonly complicated by faltering growth and pubertal delay. Pro-inflammatory cytokines are often elevated in IBD and may affect linear growth and puberty either systemically or at the level of the growth plate. Further study of the underlying mechanisms of the deleterious effects of cytokines on the growth plate may improve management of faltering growth in childhood IBD. Well-controlled clinical studies of the respective effect of nutritional support, immunomodulatory therapy, biological agents and growth and puberty promoting agents on managing faltering growth also require further attention.

Adolescent↗

PubMed2006

Biliary hypoplasia in Williams syndrome.

Neonatal hepatitis and biliary hypoplasia are not recognised features of Williams syndrome. A case of Williams syndrome, presenting with neonatal conjugated hyperbilirubinaemia leading to an initial misdiagnosis is reported.

Alagille Syndrome↗

PubMed2004

Bone mineral assessment by dual energy X-ray absorptiometry in children with inflammatory bowel disease: evaluation by age or bone area.

BACKGROUND: Abnormal linear growth and deficient bone mineral acquisition may coexist in children with inflammatory bowel disease (IBD). Traditionally, bone mineral assessment by dual energy x-ray absorptiometry (DXA) involves comparison to age- and gender-matched reference ranges, and these studies in children with IBD show a high prevalence of osteopenia. AIMS: To compare the prevalence of osteopenia using two methods of interpretation; one adjusted for age and gender and the other adjusted for bone size and gender. PATIENTS: Forty-seven patients with Crohn disease (CD) and 26 patients with ulcerative colitis (UC) with a median age of 13.5 years (range, 5.5-18.2 years) were evaluated. METHODS: Lumbar spine (LS) and total body (TB) bone mineral content (BMC) were measured by DXA and converted to bone mineral density (BMD, g/cm) corresponding to BMC divided by the bone area. Age and gender-matched BMD standard deviation scores (SDS) were based on reference data providing age- and gender-matched BMC and bone area. These data also allowed calculation of percentage of predicted bone area for age and gender (ppBone Area) and percentage of predicted BMC for Bone Area (ppBMC). RESULTS: Patients with CD were shorter than those with UC (median height, SDS, -0.9 v 0, P < 0.05). Median ppBone Area for LS and TB for the whole group was 85% (10th centile, 68; 90th centile 99) and 81% (10th centile 66; 90th centile, 97), respectively. The ppBone Area at both sites was directly related to height SDS and BMI SDS (r > 0.5; P < 0.005). Median BMD SDS for LS and TB was -1.6 (10th centile -3.6; 90th centile, -0.2) and -0.9 (10th centile, -2.4; 90th centile, 0.4), respectively. Median ppBMC for LS and TB was 98% (10th centile, 84%; 90th centile, 113%) and 101% (10th centile 94%; 90th centile, 107%), respectively. The ppBMC showed no relationship to ppBone Area (r = 0.1, NS). Failure to account for bone area led to a label of moderate or severe osteopenia in 65% of cases. After adjustment for bone area, the proportion of children with osteopenia fell to 22%. CONCLUSIONS: The data suggest that children with IBD often have small bones for age because they have growth retardation. When DXA data are interpreted with adjustment for bone size, most children were found to have adequate bone mass. Correct interpretation of DXA is important for identifying children who may be at a real risk of osteoporosis.

Absorptiometry, Photon↗