Construct validity and reliability of a French-Canadian translation of the eating in the absence of hunger questionnaire for children and adolescents.

Eating in the absence of hunger (EAH) has been associated with overweight and obesity during childhood. The gold standard to assess this behavior is a laboratory-based protocol, but a questionnaire to assess EAH more efficiently in children and adolescents has been developed and validated in English. We assessed construct validity (structural and convergent validity) and reliability (internal consistency and temporal stability) of a French translation of the EAH Questionnaire for Children and Adolescents among French-Canadian youths. We recruited participants in Montreal (Canada) aged 7-15 years old, who completed the questionnaire and provided anthropometric data. We asked participants to complete the questionnaire a second time ∼4 weeks later. The questionnaire consists of 14 questions and 3 subscales that assess EAH due to negative affect, fatigue/boredom, and external cues. We performed an exploratory factor analysis to test the factor structure and we calculated Cronbach alpha coefficients and intra-class correlations to assess internal consistency and temporal stability, respectively. We assessed associations between EAH and BMI z-score using Pearson correlations. We included 196 participants (50% girls; mean (SD) 11.9 (2.3) years old) for the first completion and 153 for the second completion. The exploratory factor analysis generated the same three subscales as the original questionnaire: negative affect (α = 0.86; ICC = 0.78), fatigue/boredom (α = 0.75; ICC = 0.70), and external cues (α = 0.68; ICC = 0.54). Participant's BMI z-scores were positively associated with the average scores from the negative affect subscale (r = 0.19; ρ = 0.009). Our results suggest that this questionnaire has an adequate construct validity, internal consistency, and temporal stability.

Assessment of the American Heart Association's "Life's simple 7" score in French-speaking adults from Québec.

BACKGROUND AND AIMS: The "Life's Simple 7" (LS7) metrics were developed by the American Heart Association (AHA) to assess and promote cardiovascular health in the American population. The purpose of this study was to assess the overall cardiovascular health of French-speaking adults from the Province of Quebec using the LS7 score. METHODS AND RESULTS: A total of 777 age and sex-representative participants of five different administrative regions in the Province of Quebec (387 men and 390 women; mean age ± SEM: 41.9 ± 0.1 years) were included in these analyses. Metrics of the LS7 score (smoking, physical activity, diet, body mass index, blood pressure, fasting total cholesterol and blood glucose) were analysed to generate a final score ranging from 0 to 7. Only 0.5% of participants met all criteria for ideal cardiovascular health. The diet metric showed the lowest prevalence of "ideal" scores (4.8%) whereas not smoking was the metric with the highest prevalence (88.1%). Women had a higher LS7 score than men, while age and education level (negative and positive association, respectively; p < 0.0001) were also associated with the LS7 score. CONCLUSION: Consistent with studies conducted among other populations, very few French-speaking adults from the Province of Quebec achieve an ideal cardiovascular health. These data indicate that further public health efforts aimed at promoting the LS7 metrics, focusing primarily on diet, are urgently needed. Specific groups, including older adults and those with lower levels of education, should be targeted when developing cardiovascular health promotion interventions.

Association of prenatal exposure to gestational diabetes with offspring body composition and regional body fat distribution.

The aim of this cohort study was to compare body composition and regional body fat distribution between children exposed (GDM+) or unexposed (GDM-) in utero to gestational diabetes mellitus (GDM) and to investigate the association with the glycaemic and the insulin profile. Data from 56 GDM+ and 30 GDM- were analysed. Height, weight and waist circumference were measured. Total and regional body composition was measured by dual-energy X-ray absorptiometry. Insulin, glucose and HbA1c were obtained from a fasting plasma sample, and the HOMA-IR index was calculated. anova was performed to compare adiposity measures between GDM+ and GDM-. Associations between the glycaemic and insulin profile and adiposity measures were studied using partial Pearson correlations. Mean age was 6.6 ± 2.3 years. Waist circumference, fat mass percentage, android fat mass, android fat mass percentage and android-to-gynoid fat mass ratio were higher among GDM+, and lean mass percentage was lower (P < 0.05). Among GDM+ children, body mass index (BMI) z score, waist circumference, fat mass percentage, android fat mass percentage and android-to-gynoid fat mass ratio were all positively correlated with HbA1C (r = 0.32-0.43, P < 0.05). Prenatal exposure to GDM is associated with increased total and abdominal adiposity. This increased adiposity observed among GDM+ children is associated with an altered glycaemic profile. This study is registered in the Clinical Trials.gov registry (NCT01340924).

Influence of maternal physical activity on infant's body composition.

BACKGROUND: Physical activity (PA) during pregnancy might contribute to reduce neonatal adiposity, a predictor of metabolic disturbances. OBJECTIVE: The objective of the study was to evaluate the association between maternal PA intensity and neonatal body composition. METHODS: Maternal PA measured by accelerometry and nutrition were documented during pregnancy, as well as neonatal body composition by dual-energy X-ray absorptiometry following delivery. Associations between PA at 17 and 36 weeks (time spent in moderate PA (MPA), vigorous PA (VPA) status and their interaction) and neonatal body composition were addressed by multivariate regression analyses. RESULTS: From 104 women, 50 (48%) and 16 (18%) performed VPA at 17 and 36 weeks of pregnancy. Performing VPA at either time was associated with a decreased birthweight (BW), while only VPA at 17 weeks decreased neonatal adiposity (fat percentage: -2.3 ± 0.8%, p = 0.003). MPA at 36 weeks was associated with an increased lean mass (2.0 ± 0.8 g per min day-1 , p = 0.012). Significant interactions were found for BW and bone mineral content (BMC). MPA at 17 weeks tended to increase BW, but not BMC, in the no VPA strata. By contrast, high levels of MPA (≥112 min d-1 ) combined with VPA at 17 weeks reduced neonatal BMC and BW compared with no VPA (BMC: -5.4 ± 2.0 g, p = 0.008, BW: -302.8 ± 83.7 g, p = 0.0003). Differences were not significant with low MPA levels. CONCLUSIONS: Exercise intensity modulates neonatal body composition. The long-term significance of a reduced BW, adiposity and BMC with VPA requires further study.

An explained variance-based genetic risk score associated with gestational diabetes antecedent and with progression to pre-diabetes and type 2 diabetes: a cohort study.

OBJECTIVE: To determine whether an explained-variance genetic risk score (GRS), with 36 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes (T2D), is also associated with gestational diabetes mellitus (GDM), and with the progression to pre-diabetes and T2D among women with prior GDM. DESIGN: A cohort study. SETTING: Clinical investigation unit of Laval University, Quebec, Canada. POPULATION: A cohort of 214 women with prior GDM and 82 controls recruited between 2009 and 2012. METHODS: Associations between the GRS and GDM. MAIN OUTCOMES MEASURES: GDM and prevalence of pre-diabetes and T2D. RESULTS: Women with prior GDM had a higher GRS compared with controls (38.6 ± 3.9, 95% CI 38.1-39.1, versus 37.4 ± 3.2, 95% CI 36.7-38.1; P < 0.0001). In women with prior GDM, the explained-variance GRS was higher for pre-diabetic women compared with women who remained normoglucotolerant at testing (1.21 ± 0.18, 95% CI 1.18-1.23, versus 1.17 ± 0.15, 95% CI 1.13-1.20; P < 0.0001). Similarly, women with T2D had a higher explained-variance GRS compared with women with prior GDM who remained normoglucotolerant (1.20 ± 0.18, 95% CI 1.14-1.25, versus 1.17 ± 0.17, 95% CI 1.13-1.20; P < 0.0001). The predictive effects of the explained-variance GRS, age, and body mass index (BMI), or the additive effects of the three variables, were tested for pre-diabetes and T2D. We observed an area under the curve of 0.6269 (95% CI 0.5638-0.6901) for age and BMI, and adding the explained-variance GRS into the model increased the area to 0.6672 (95% CI 0.6064-0.7281) for the prediction of pre-diabetes. CONCLUSIONS: An explained-variance GRS is associated with both GDM and progression to pre-diabetes and T2D in women with prior GDM.

Nutrigenomics - perspectives from registered dietitians: a report from the Quebec-wide e-consultation on nutrigenomics among registered dietitians.

BACKGROUND: Not all healthcare professionals are familiar with nutrigenomics. However, they recognise that nutrigenomics has great potential for the development of preventive health approaches. The present study aimed to provide an overall picture of the current situation about nutrigenomics in the practice of registered dietitians (RDs) from the province of Quebec (Canada). METHODS: Three hundred and seventy-three RDs members of the Ordre professionnel des diététistes du Québec completed an online survey that included 34 questions, most of which were closed-ended questions. RESULTS: Overall, 76.9% of RDs knew about nutrigenomics. Among RDs with <5 years of experience, 49.2% knew about genetic testing related to nutrition compared to 11.7% for RDs with over 25 years of experience. Currently, 75.9% of RDs working in clinical nutrition in the public sector consider that they do not have the basic knowledge to integrate nutrigenomics in their practice compared to 62.9% for RDs in private practice. When asked about main limitations of genetic testing related to nutrition, RDs considered that genetic testing does not consider the other determinants of health, that genetic testing and their results have poor accuracy, and that there is a lack of scientific evidence. Concerns remained about ethical and legal aspects and its difficult application as a result of poor understanding and/or interpretation by professionals and/or customers. The high costs of these tests were also noted as a limitation. CONCLUSIONS: Registered dietitians know and are interested in nutrigenomics, especially those with less experience, although they do not feel adequately qualified to integrate findings from nutrigenomics into their practice.

Risks of nutrigenomics and nutrigenetics? What the scientists say.

Nutrigenomics and nutrigenetics (hereafter NGx) have stimulated expectations for beneficial applications in public health and individuals. Yet, the potential achievability of such promise is not without socioethical considerations that challenge NGx implementation. This paper focuses on the opinions of NGx researchers about potential risks raised by NGx. The results of an online survey show that these researchers (n = 126) are fairly confident about the potential benefits of NGx, and that most downplay its potential risks. Researchers in this field do not believe that NGx will reconfigure foods as medication or transform the conception of eating into a health hazard. The majority think that NGx will produce no added burden on individuals to get tested or to remain compliant with NGx recommendations, nor that NGx will threaten individual autonomy in daily food choice. The majority of researchers do not think that NGx will lead to discrimination against and/or stigmatization of people who do not comply with NGx dietary recommendations. Despite this optimism among NGx researchers, we suggest that key risk factors raised by the socioethical context in which NGx applications will be implemented need to be considered.

Health-related direct-to-consumer genetic tests: a public health assessment and analysis of practices related to Internet-based tests for risk of thrombosis.

BACKGROUND: Recent years have seen increased concern about direct-to-consumer (DTC) genetic testing (i.e., the sale and use of genetic tests without involving a health care provider). Numerous professional organizations have developed policies in this area. However, little systematic evidence exists to inform public policy about these tests. METHODS: We conducted a systematic search to identify genetic tests that are sold DTC without involving a health care provider. We evaluated the practices of companies offering DTC genetic tests for risk of thrombosis using criteria from multiple sources and a minimal set of key practices. RESULTS: We identified 84 instances of currently available health-related DTC genetic tests sold on 27 Web sites; the most common were for pharmacogenomics (12), risk of thrombosis (10), and nutrigenomics (10). For the DTC genetic tests for risk of thrombosis, we found low adherence to recommendations. Online information was frequently incomplete and had low agreement with professional recommendations. CONCLUSION: Our findings document the rapid growth in the availability of health-related DTC genetic tests and highlight the need to improve the delivery of DTC genetic tests. A major implication of this study is the need for the scientific and medical community to develop consistent recommendations to increase their impact.

Features of the metabolic syndrome are modulated by an interaction between the peroxisome proliferator-activated receptor-delta -87T>C polymorphism and dietary fat in French-Canadians.

OBJECTIVE: We verified whether genetic variants in this gene are associated with the MS and whether dietary fatty acids interact with the -87T>C polymorphism. METHODS: By direct sequencing, we identified 15 variants in the PPAR-delta gene and analyses were pursued with the -87T>C polymorphism for 340 subjects. RESULTS: Metabolic variables were comparable among each genotype group. The -87T>C polymorphism, fat intake and the interaction accounted, respectively for 2.2, 1.9 and 1.5% of the variance in high-density lipoprotein cholesterol (HDL-C) levels (P<0.05) (age, sex and energy intake were included into the model). The total cholesterol/HDL-C ratio was also modulated by a gene-diet interaction and by the -87T>C polymorphism (P<0.05). No gene-diet interaction effects were observed for other features of the MS. The age- and sex-adjusted odds ratio (OR) of exhibiting three or more features of the MS when carrying the -87C allele was 0.62 (P=0.04) compared to -87T/T. However, in subjects consuming less than 34.4% of energy from fat (median of fat consumption), the OR in carriers of the -87C allele was of 0.42 (P=0.008). CONCLUSION: These data suggest that the PPAR-delta -87T>C polymorphism may be associated with a lower risk to exhibit the MS and this association is influenced by dietary fat intake. The metabolic syndrome (MS) is influenced by genetic and environmental factors. Peroxisome proliferator-activated receptor delta (PPAR-delta), a transcription factor involved in lipid metabolism, is a candidate gene for the MS.

Plasma concentrations of apolipoprotein B are modulated by a gene--diet interaction effect between the LFABP T94A polymorphism and dietary fat intake in French-Canadian men.

Hyperapobetalipoproteinemia is a common feature of the metabolic syndrome and could result from the interaction between genetic and dietary factors. The objective of this study was to verify whether dietary fat intake interacts with the T94A polymorphism of the liver fatty acid-binding protein (LFABP) gene to modulate plasma apolipoprotein (apo) B levels. Dietary fat and saturated fat intakes were obtained by a dietitian-administered food frequency questionnaire and the LFABP T94A genotype was determined by a PCR-RFLP based method in 623 French-Canadian men recruited through the Chicoutimi Lipid Clinic (279 T94/T94, 285 T94/A94, and 59 A94/A94). The LFABP T94A polymorphism was not associated with plasma apo B levels when fat intake was not taken into consideration. However, in a model including the polymorphism, fat intake expressed as a percentage of total energy intake, the interaction term and covariates, the variance in apo B concentrations was partly explained by the LFABP T94A polymorphism (5.24%, p = 0.01) and by the LFABP T94A*fat interaction (6.25%, p = 0.005). Results were similar when saturated fat replaced fat intake in the model (4.49%, p = 0.02 for LFABP T94A and 6.43%, p = 0.004 for the interaction). Moreover, in men consuming more than 30% of energy from fat, the odds ratio for having plasma apo B levels above 1.04 g/L for A94 carriers was of 0.40 (p = 0.02) compared to T94/T94 homozygotes. Results were similar for carriers of the A94 allele consuming more than 10% of energy from saturated fat (OR: 0.32, p = 0.005). In conclusion, T94/T94 exhibit higher apo B levels whereas carriers of the A94 allele seem to be protected against high apo B levels when consuming a high fat and saturated fat diet. These findings reinforce the importance to take into account gene-diet interactions in the prevention and management of the metabolic syndrome.

Clinical variability in maternally inherited leber hereditary optic neuropathy with the G14459A mutation.

Spasticity and dystonia have been associated with mitochondrial (mt) DNA mutations at A11696G, G14459A, and T14596A. We describe the clinical features and molecular analysis of two Caucasian pedigrees with the 14,459 guanosine (G) --> adenine (A) transition. The maternally inherited Leber hereditary optic neuropathy (LHON) phenotypes showed extreme clinical variability and the only screening test that was abnormal in the patient with spasticity/dystonia was a high T2 signal in the putamen bilaterally. The male patient in the second pedigree showed features of optic neuropathy without spasticity/dystonia. These results further support that the 14,459 G --> A transition mutation is causally related to LHON and spasticity/dystonia.

The PPAR-gamma P12A polymorphism modulates the relationship between dietary fat intake and components of the metabolic syndrome: results from the Québec Family Study.

The metabolic syndrome is a complex disorder characterized by an atherogenic dyslipidemia resulting from the interaction between genetic and nutritional factors. The objective of this study was to examine in a cohort of 720 adults participating in the Québec Family Study (QFS) whether dietary fat interacts with the P12A polymorphism in the gene encoding the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear factor that regulates lipid and glucose homeostasis. Carriers of the A12 allele had a higher body mass index (BMI), waist circumference, fat mass as well as subcutaneous adipose tissue and visceral adipose tissue (VAT) areas both assessed by computed tomography than P12/P12 homozygotes. Total fat and saturated fat intakes estimated from a 3-day food record were significantly correlated with several components of the metabolic syndrome in P12/P12 homozygotes. None of these expected associations were observed among carriers of the A12 allele. Furthermore, in a model including the PPAR-gamma P12A polymorphism, fat intake, age and gender, PPAR-gamma P12A and its interaction with fat intake were associated with BMI and waist circumference. Similar results were obtained when saturated fat intake replaced total fat intake into the model. When the two genotype groups were further classified into quartiles of total fat or saturated fat intake and their characteristics compared, an increase in fat intake was associated with an increase in waist circumference in P12/P12 homozygotes but not in A12 carriers. There was no difference in the waist circumference in carriers of the A12 allele whether the fat or the saturated fat intake was high or low. These results suggest that the PPAR-gamma P12A polymorphism can modulate the association between dietary fat intake and components of the metabolic syndrome.

Genetic variation and structure of fisher (Martes pennanti) populations across North America.

Fishers are mid-sized forest carnivores indigenous to North America that experienced sharp population declines from the early 1800s through to the mid-1900s. To evaluate levels of genetic variation within and subdivision among northern fisher populations 459 individuals were genotyped using 13 microsatellite loci. Genetic diversity was found to be slightly lower in re-introduced populations than in adjacent indigenous populations. Furthermore, fisher populations revealed much more genetic structuring than two closely related mustelids. Further investigation is needed to determine if fishers are more philopatric than martens and wolverines or if barriers to dispersal explain the levels of structure identified in this study.

Exfoliation syndrome: clinical and genetic features.

We have ascertained a large number of individuals and families with exfoliation syndrome in order to clarify the disorder's mode of inheritance. Patients with exfoliation syndrome and their relatives were recruited from the practices of a group of ophthalmologists in Maritime Canada. The degree to which the subjects were affected was graded according to a standardized 1-4-point clinical scheme. Pedigrees were constructed from information supplied by family members and from genealogical sources. A total of 782 patients and relatives participated, of whom 467 were definitely affected. The mean age of affected males and females did not differ significantly, but females appeared to be more severely affected at ascertainment than males. More than half of the affected subjects had definite exfoliation in only one eye. Approximately 30 multiplex families were discovered, including one containing 23 affected members among a total of 137 examined individuals that constitutes the largest exfoliative pedigree thus far described. We observed well-documented paternal transmission of the trait, a finding that has not to our knowledge been previously reported. Clustering of cases in the families provides evidence for the involvement of genetic factors. The possibility of homozygosity is suggested in a few patients by the earlier or more frequent presentation of the disorder in the offspring of two affected parents or consanguineous pairings. Although a multifactorial mode of inheritance cannot be excluded, exfoliation syndrome appears to be inherited as an autosomal dominant trait whose late onset and incomplete penetrance poses a significant but not insuperable obstacle to pedigree construction.

A summary of 20 CACNA1F mutations identified in 36 families with incomplete X-linked congenital stationary night blindness, and characterization of splice variants.

Incomplete X-linked congenital stationary night blindness (CSNB) is a recessive, non-progressive eye disorder characterized by abnormal electroretinogram and psychophysical testing and can include impaired night vision, decreased visual acuity, myopia, nystagmus, and strabismus. Including the 20 families previously reported (Bech-Hansen et al. 1998b), we have now analyzed patients from a total of 36 families with incomplete CSNB and identified 20 different mutations in the calcium channel gene CACNA1F. Three of the mutations account for incomplete CSNB in two or more families, and a founder effect is clearly demonstrable for one of these mutations. Of the 20 mutations identified, 14 (70%) are predicted to cause premature protein truncation and six (30%) to cause amino acid substitutions or deletions at conserved positions in the alpha1F protein. In characterizing transcripts of CACNA1F we have identified several splice variants and defined a prototypical sequence based on the location of mutations in splice variants and comparison with the mouse orthologue, Cacnalf.

Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia.

CONTEXT: Human papillomavirus (HPV) infection is believed to be the central cause of cervical cancer, although most of the epidemiological evidence has come from retrospective, case-control studies, which do not provide information on the dynamics of cumulative or persistent exposure to HPV infection. OBJECTIVE: To assess the risks of cervical neoplasia related to prior persistent HPV infections. DESIGN AND SETTING: Longitudinal study of the natural history of HPV infection and cervical neoplasia in women residing in the city of São Paulo, Brazil, which was conducted between November 1993 and March 1997 and involved repeated measurements of HPV and lesions with follow-up until June 2000. PARTICIPANTS: A total of 1611 women with no cytological lesions at enrollment and HPV test results available from the first 2 visits. MAIN OUTCOME MEASURE: Cervical specimens taken for Papanicolaou cytology and HPV testing every 4 months in the first year and twice yearly thereafter. Incident cervical cancer precursor lesions ascertained by expert review of all cytology smears. RESULTS: The incidence rate of squamous intraepithelial lesions (SILs) was 0.73 per 1000 women-months (95% confidence interval [CI], 0.5-0.9) among women free of HPV at the 2 initial visits and 8.68 (95% CI, 2.3-15.1) among women with HPV type 16 or 18 infections persisting over both visits. Relative to those negative for HPV oncogenic types at both initial visits, the relative risk (RR) of incident SIL was 10.19 (95% CI, 5.9-17.6) for persistent infections with any known oncogenic HPV types. The equivalent RR of incident high-grade SIL was 11.67 (95% CI, 4.1-33.3). The RRs of lesions were considerably higher for persistent infections with HPV type 16 or 18. CONCLUSION: A strong relationship exists between persistent HPV infections and SIL incidence, particularly for HPV types 16 and 18.

Comparison of expression patterns and cell adhesion properties of the mouse biliary glycoproteins Bbgp1 and Bbgp2.

Biliary glycoproteins are members of the carcinoembryonic antigen (CEA) family and behave as cell adhesion molecules. The mouse genome contains two very similar Bgp genes, Bgp1 and Bgp2, whereas the human and rat genomes contain only one BGP gene. A Bgp2 isoform was previously identified as an alternative receptor for the mouse coronavirus mouse hepatitis virus. This isoform consists of two extracellular immunoglobulin domains, a transmembrane domain and a cytoplasmic tail of five amino acids. In this report, we have examined whether the Bgp2 gene can express other isoforms in different mouse tissues. We found only one other isoform, which has a long cytoplasmic tail of 73 amino acids. The long cytodomain of the Bgp2 protein is highly similar to that of the Bgp1/4L isoform. The Bgp2 protein is expressed in low amounts in kidney and in a rectal carcinoma cell line. Antibodies specific to Bgp2 detected a 42-kDa protein, which is expressed at the cell surface of these samples. Bgp2 was found by immunocytochemistry in smooth muscle layers of the kidney, the uterus, in gut mononuclear cells and in the crypt epithelia of intestinal tissues. Transfection studies showed that, in contrast with Bgp1, the Bgp2 glycoprotein was not directly involved in intercellular adhesion. However, this protein is found in the proliferative compartment of the intestinal crypts and in cells involved in immune recognition. This suggests that the Bgp2 protein represents a distinctive member of the CEA family; its unusual expression patterns in mouse tissues and the unique functions it may be fulfilling may provide novel clues about the multiple functions mediated by a common BGP protein in humans and rats.

Four polymorphic variations in the PEDF gene identified during the mutation screening of patients with Leber congenital amaurosis.

PURPOSE: Leber congenital amaurosis (LCA) has been mapped to chromosome 17p13.1. From the candidate genes mapped to this region, thus far, only Retinal Guanylate Cyclase (RetGC), has been found to have pathogenic LCA mutations, in families from North African origin. However, early reports, demonstrated eight LCA families linked to 17p13.1, but only four of them showed mutations in RetGC. Mapped in proximity to this locus is the candidate gene Pigment Epithelium Derived actor (PEDF), a factor implicated in photoreceptor differentiation and neuronal survival. Our purpose in this study was to identify mutations and polymorphisms in the PEDF gene in LCA patients of diverse ethnic origin. METHODS: Automated genotyping with four 17p13.1 markers flanking the PEDF gene was performed to assess homozygosity and PCR-SSCP combined with direct sequencing was used to detect mutations in the PEDF gene in 17 LCA patients. RESULTS: Homozygosity of markers D17S796 and D17S804 was found and four new intragenic basepair alterations were discovered: a Met72Thr polymorphism in exon 3 (T331C), a Thr130Thr polymorphism in exon 4 (T506C), a G to A transition in intron 5 (nine base pairs upstream from splice acceptor site), and a Tyr321Tyr polymorphism in exon 7 (C1079T) were detected. CONCLUSIONS: We report the discovery of four new polymorphic alterations in the PEDF gene in LCA patients and exclude by RFLP analysis the PEDF gene as a common cause of Leber congenital amaurosis. These single nucleotide polymorphisms will aid in future linkage analysis of complex multifactorial diseases involving retinal and RPE dysfunctions.

Association of biliary glycoprotein with protein tyrosine phosphatase SHP-1 in malignant colon epithelial cells.

Biliary glycoprotein (Bgp) is a member of the immunoglobulin superfamily and the carcinoembryonic antigen family. Previous studies have shown that Bgp functions as an intercellular adhesion molecule and a canalicular bile salt transporter. Moreover, we and others demonstrated that Bgp can inhibit colonic and prostatic tumor cell growth in vivo, through a mechanism which depends on sequences present in its cytoplasmic domain. In this study, we have examined the possibility that the cytoplasmic domain of Bgp can interact with signal transduction molecules. We showed that tyrosine phosphorylated Bgp, expressed in mouse colon carcinoma CT51 cells, could reversibly associate with protein tyrosine phosphatase SHP-1. Mutation of either of two tyrosine residues present in the cytoplasmic domain of Bgp abrogated SHP-1 binding, suggesting that this association was mediated by both tyrosine residues. Similarly, we noted that either of the two SH2 domains of SHP-1 could bind tyrosine phosphorylated Bgp in vitro. It is therefore conceivable that some of the functions of Bgp are mediated through its ability to induce intracellular protein tyrosine dephosphorylation.