ABSTRACT
AIMS/HYPOTHESIS: Insulin-requiring diabetes affects 25-50% of young adults with cystic fibrosis (CF). Although the cause of diabetes in CF is unknown, recent heritability studies in CF twins and siblings indicate that genetic modifiers play a substantial role. We sought to assess whether genes conferring risk for diabetes in the general population may play a risk modifying role in CF. METHODS: We tested whether a family history of type 2 diabetes affected diabetes risk in CF patients in 539 families in the CF Twin and Sibling family-based study. A type 2 diabetes susceptibility gene (transcription factor 7-like 2, or TCF7L2) was evaluated for association with diabetes in CF using 998 patients from the family-based study and 802 unrelated CF patients in an independent case-control study. RESULTS: Family history of type 2 diabetes increased the risk of diabetes in CF (OR 3.1; p = 0.0009). A variant in TCF7L2 associated with type 2 diabetes (the T allele at rs7903146) was associated with diabetes in CF in the family study (p = 0.004) and in the case-control study (p = 0.02; combined p = 0.0002). In the family-based study, variation in TCF7L2 increased the risk of diabetes about three-fold (HR 1.75 per allele, 95% CI 1.3-2.4; p = 0.0006), and decreased the mean age at diabetes diagnosis by 7 years. In CF patients not treated with systemic glucocorticoids, the effect of TCF7L2 was even greater (HR 2.9 per allele, 95% CI 1.7-4.9, p = 0.00011). CONCLUSIONS/INTERPRETATION: A genetic variant conferring risk for type 2 diabetes in the general population is a modifier of risk for diabetes in CF.
Subject(s)
Cystic Fibrosis/genetics , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , TCF Transcription Factors/genetics , Adolescent , Adult , Child, Preschool , Cystic Fibrosis/drug therapy , Cystic Fibrosis/epidemiology , Cystic Fibrosis/surgery , DNA/genetics , Family , Female , Genetic Variation , Glucocorticoids/therapeutic use , Humans , Infant , Lung Transplantation , Male , Odds Ratio , Prevalence , Respiratory Function Tests , Risk Factors , Siblings , Surveys and Questionnaires , Transcription Factor 7-Like 2 ProteinABSTRACT
Schwannomas usually present as solitary subcutaneous tumors adherent to a peripheral nerve. A solitary cutaneous schwannoma presenting as a solitary cutaneous nodule on the foot of a 19-year-old male is described. This is an unusual presentation of schwannoma. Saucerized excision produced an excellent result with no adverse effect on function or cutaneous sensation.
Subject(s)
Foot Diseases/pathology , Neurilemmoma/pathology , Skin Neoplasms/pathology , Adult , Foot Diseases/surgery , Humans , Male , Neurilemmoma/surgery , Skin Neoplasms/surgeryABSTRACT
A number of deletion mutants of the hepatitis B viral X antigen had been constructed and assayed for their ability to transactivate heterologous viral regulatory elements. Neither the N-terminal nor the C-terminal amino acid residues were required for transactivating activity. Transactivating activity that resided within amino acid residues 32 to 148 of the X antigen did not show any target DNA sequence or cell line specificity.
Subject(s)
Hepatitis B virus/genetics , Trans-Activators/genetics , Cloning, Molecular , DNA Mutational Analysis , Gene Expression Regulation, Viral , Restriction Mapping , Structure-Activity Relationship , Viral Regulatory and Accessory ProteinsABSTRACT
Infection with Toxoplasma gondii, which occurs in both men and women, is usually subclinical and benign. Infection during pregnancy, however, may be a serious and even life-threatening event for the fetus. Antenatal education should focus on avoidance of contact with the sources of infection: the domestic cat and raw or rare meats. A review of toxoplasmosis is presented, and means for its primary prevention through antenatal education are outlined.