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Biomedical subjects

Peter Green

Publications and source records attributed to Peter Green.

8 recordsLinked to original sources

Investigation of association of the DLG5 gene with phenotypes of inflammatory bowel disease in the British population.

BACKGROUND AND AIMS: Mutations in the DLG5 gene are associated with an increased risk of inflammatory bowel disease (IBD) in some European populations. Initial investigation of a British IBD population showed evidence of association of one of three DLG5 variants, R30Q, in a family-based collection but not in a case-control cohort. We have now examined the association of the R30Q polymorphism in a large cohort of British IBD cases, tested for interaction between the DLG5 and CARD15 genes and assessed possible association of DLG5 with clinical features of Crohn's disease (CD) and ulcerative colitis (UC). MATERIALS AND METHODS: DLG5 R30Q and the CARD15 polymorphisms, Arg702Trp, Gly908Arg and Leu1007fs were genotyped in 1,148 IBD cases and 749 controls. DLG5 R30Q was also analysed in cases stratified by CARD15 genotype, disease subtype and smoking history. RESULTS/FINDINGS: No significant difference in frequencies of the R30Q variant was observed between IBD cases (9.9%) and controls (10.1%) or in cases analysed separately as CD and UC. There was also no significant difference in the frequency of R30Q between CD cases carrying risk-associated CARD15 alleles and those that did not. The frequency of R30Q was higher in CD cases with ileal disease than cases without (p=0.042) and higher in CD cases who had smoked than in nonsmokers (p=0.009). INTERPRETATION/CONCLUSION: The R30Q variant in the DLG5 gene does not appear to be associated with an overall increase in the risk of disease in a British IBD cohort, but differences in its frequency in subgroups of CD patients warrant further investigation.

Case-Control Studies↗

A second form of collagenous lectin from the tunicate, Styela plicata.

This study characterised a 90 kDa lectin from an invertebrate chordate, the tunicate Styela plicata. One- and two-dimensional electrophoresis showed that the apparent molecular weight of this protein is maintained under both reducing and non-reducing conditions, suggesting that its native form is a monomer. The 90 kDa lectin was localised within a single type of hemocyte (morula cells), but was secreted from those cells when tunicates were challenged with the inflammatory elicitor, zymosan. Functional studies showed that the 90 kDa protein binds to galactose-based sugars in a divalent cation-dependent manner. Amino acid composition analysis and N-terminal amino acid sequencing indicated that the 90 kDa lectin is related to a previously characterised, collagenous lectin from S. plicata, splic43. However, peptide mass fingerprinting identified numerous differences between the two proteins. This suggests that the 90 kDa molecule represents a novel protein that is involved in host defence.

Animals↗

Assaying chromosomal inversions by single-molecule haplotyping.

Inversions are an important form of structural variation, but they are difficult to characterize, as their breakpoints often fall within inverted repeats. We have developed a method called 'haplotype fusion' in which an inversion breakpoint is genotyped by performing fusion PCR on single molecules of human genomic DNA. Fusing single-copy sequences bracketing an inversion breakpoint generates orientation-specific PCR products, exemplified by a genotyping assay for the int22 hemophilia A inversion on Xq28. Furthermore, we demonstrated that inversion events with breakpoints embedded within long (>100 kb) inverted repeats can be genotyped by haplotype-fusion PCR followed by bead-based single-molecule haplotyping on repeat-specific markers bracketing the inversion breakpoint. We illustrate this method by genotyping a Yp paracentric inversion sponsored by >300-kb-long inverted repeats. The generality of our methods to survey for, and genotype chromosomal inversions should help our understanding of the contribution of inversions to genomic variation, inherited diseases and cancer.

Chromosome Inversion↗

Lipoatrophy in patients with multiple sclerosis on glatiramer acetate.

BACKGROUND: Patients with relapsing remitting multiple sclerosis on the disease modifying therapy of glatiramer acetate may be experiencing an adverse reaction of lipoatrophy at the sites of their subcutaneous injections. The purpose of this study was to complete a full examination of the injection site areas for users of glatiramer acetate, and to examine the relationship between lipoatrophy and patient characteristics. METHODS: Glatiramer acetate users were identified by means of chart review. Over six months, during regular clinic appointments, assessment included a full examination of injection site areas including visual inspection and manual palpation. Additional patient and clinical characteristics were obtained by means of chart review and patient questioning. RESULTS: Seventy-six patients had been or were current users of glatiramer acetate. Of these, 34 (45%) had evidence of lipoatrophy in at least one injection site area. All were female, and five had severe, nine had moderate and 20 had mild lipoatrophy. In some cases, lipoatrophy occurred within months of therapy initiation. Case reviews are included for five of the 34 patients, along with photographs of the lipoatrophy, a magnetic resonance image and comments on skin biopsies. CONCLUSIONS: Prevalence of lipoatrophy was much higher than expected. Possible reasons for this adverse reaction are explored and suggested treatment recommendations are reviewed. Lipoatrophy can be very disfiguring and is thought to be permanent, and the psychological impact can be significant. It is, therefore, important that patients be aware of the possibility of lipoatrophy, be able to identify it and discontinue injecting in areas where it is identified.

Adult↗

Pluralistic ignorance and college student perceptions of gender-specific alcohol norms.

Students' perceived norms and personal concern about alcohol use were examined in 4 (N=971) experiments. Men reported that same-sex peers were less concerned about campus alcohol practices than themselves or female students; women believed that they were more concerned about campus alcohol practices than both same- and opposite-sex peers (Experiments 1 and 2). Additional evidence suggested that students were not merely engaging in impression management. Men reported more social pressure to drink and greater embarrassment about expressing drinking-related concerns; women expected more severe consequences if they drank excessively (Experiment 3). A male student (vs female student) expressing concerns about alcohol was believed to experience greater difficulties fitting in (Experiment 4). Implications for peer influence and drug use intervention are discussed.

Adult↗

Genomewide linkage analysis of celiac disease in Finnish families.

Celiac disease (CD), or gluten-sensitive enteropathy, is a common multifactorial disorder resulting from intolerance to cereal prolamins. The only established genetic susceptibility factor is HLA-DQ, which appears to explain only part of the overall genetic risk. We performed a genomewide scan of CD in 60 Finnish families. In addition to strong evidence for linkage to the HLA region at 6p21.3 (Z(max)>5), suggestive evidence for linkage was found for six other chromosomal regions--1p36, 4p15, 5q31, 7q21, 9p21-23, and 16q12. We further analyzed the three most convincing regions--4p15, 5q31, and 7q21--by evaluation of dense marker arrays across each region and by analysis of an additional 38 families. Although multipoint analysis with dense markers provided supportive evidence (multipoint LOD scores 3.25 at 4p15, 1.49 at 5q31, and 1.04 at 7q21) for the initial findings, the additional 38 families did not strengthen evidence for linkage. The role that HLA-DQ plays was studied in more detail by analysis of DQB1 alleles in all 98 families. All but one patient carried one or two HLA-DQ risk alleles, and 65% of HLA-DQ2 carriers were affected. Our study indicates that the HLA region harbors a predominant CD-susceptibility locus in these Finnish families.

Adult↗