In this study, we screened a large cohort of subjects with increased risk for diabetes and identified two subjects with impaired glucose tolerance carrying common, heterozygous, missense mutations in the PDX1 coding region leading to single amino acid exchanges (P33T, C18R) in its transactivation domain.
Generation of a human induced pluripotent stem cell (iPSC) line from a patient with family history of diabetes carrying a C18R mutation in the PDX1 gene.
Generation of a human induced pluripotent stem cell (iPSC) line from a patient with family history of diabetes carrying a C18R mutation in the PDX1 gene.
Three variants (C18R, Q59L and D76N) were screened by PCR-RFLP in a group of 296 unrelated French late-onset type 2 diabetic subjects consecutively recruited in a diabetes department of a university hospital, regardless of family history of diabetes.
Three variants (C18R, Q59L and D76N) were screened by PCR-RFLP in a group of 296 unrelated French late-onset type 2 diabetic subjects consecutively recruited in a diabetes department of a university hospital, regardless of family history of diabetes.
Three variants (C18R, Q59L and D76N) were screened by PCR-RFLP in a group of 296 unrelated French late-onset type 2 diabetic subjects consecutively recruited in a diabetes department of a university hospital, regardless of family history of diabetes.
Three variants (C18R, Q59L and D76N) were screened by PCR-RFLP in a group of 296 unrelated French late-onset type 2 diabetic subjects consecutively recruited in a diabetes department of a university hospital, regardless of family history of diabetes.
The lower penetrance D76N and Q59L mutations were more prevalent and were associated with a relative risk of 12.6 for diabetes and with decreased glucose-stimulated insulin-secretion in nondiabetic subjects.
The lower penetrance D76N and Q59L mutations were more prevalent and were associated with a relative risk of 12.6 for diabetes and with decreased glucose-stimulated insulin-secretion in nondiabetic subjects.
In this study, we screened a large cohort of subjects with increased risk for diabetes and identified two subjects with impaired glucose tolerance carrying common, heterozygous, missense mutations in the PDX1 coding region leading to single amino acid exchanges (P33T, C18R) in its transactivation domain.
In this study, we screened a large cohort of subjects with increased risk for diabetes and identified two subjects with impaired glucose tolerance carrying common, heterozygous, missense mutations in the PDX1 coding region leading to single amino acid exchanges (P33T, C18R) in its transactivation domain.
Longitudinal analysis with a generalized estimating equation and with adjustment for age, gender, body mass index and smoking status revealed that rs2116519 of family with sequence similarity 78, member B (FAM78B; P=0.0266), rs6929846 of butyrophilin, subfamily 2, member A1 (BTN2A1; P=0.0013), rs146021107 of pancreatic and duodenal homeobox 1 (PDX1; P=0.0031) and rs1671021 of lethal giant larvae homolog 2 (Drosophila) (LLGL2; P=0.0372) were significantly (P<0.05) associated with the prevalence of hypertension.
Anterior gradient protein-2 and S100P were frequently expressed in perihilar CCA and PDAC, while neural cell adhesion molecule and luminal epithelial membrane antigen were common in CCA components of c-HC-CCA.
In contrast to other reported PDX1 mutations leading to neonatal diabetes and pancreas agenesis, homozygosity for the E178G mutation was not associated with clinical signs of exocrine pancreas insufficiency.
Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the G-->A (Ser89Asn) polymorphism of UTS2 [odds ratio (OR), 1.90; 95% confidence interval (CI), 1.18-3.08], the 2445G-->A (Ala54Thr) polymorphism of FABP2 (OR, 1.72; 95% CI, 1.23-2.40), the -11377C-->G polymorphism of ADIPOQ (OR, 1.43; 95% CI, 1.15-1.79), the -231A-->G polymorphism of EDNRA (OR, 0.65; 95% CI, 0.48-0.89), and the -108/3G-->4G polymorphism of PDX1 (OR, 0.64; 95% CI, 0.48-0.87) were significantly (P<0.05) associated with MI.
The Chi-square test, multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of hypertension, hypercholesterolemia, and diabetes mellitus, as well as a stepwise forward selection procedure revealed that the 2445G-->A (Ala54Thr) polymorphism (rs1799883) of FABP2, the -108/3G-->4G polymorphism of IPF1 (S82168), the A-->G (Thr94Ala) polymorphism (rs2241883) of FABP1, the G-->A (Asp2213Asn) polymorphism (rs529038) of ROS1, the -11377C-->G polymorphism (rs266729) of ADIPOQ, the 162A-->C polymorphism (rs4769055) of ALOX5AP, the -786T-->C polymorphism (rs2070744) of NOS3, and the 3279C-->T polymorphism (rs7291467) of LGALS2 were associated (P<0.05) with the prevalence of atherothrombotic cerebral infarction.
Genotypes for these polymorphisms, especially for the 2445G-->A (Ala54Thr) polymorphism of FABP2, may prove informative for the prediction of genetic risk for atherothrombotic cerebral infarction among such individuals.
Our findings suggest that the P33T IPF1 mutation may provide an increased susceptibility to the development of gestational diabetes and MODY4 in the Italy-6 pedigree.
The E224K mutation cosegregated with early-onset diabetes or impaired glucose tolerance in a large family, suggestive of the type 4 form of maturity-onset diabetes of the young rather than type 2 diabetes.
The E224K mutation cosegregated with early-onset diabetes or impaired glucose tolerance in a large family, suggestive of the type 4 form of maturity-onset diabetes of the young rather than type 2 diabetes.
The E224K mutation cosegregated with early-onset diabetes or impaired glucose tolerance in a large family, suggestive of the type 4 form of maturity-onset diabetes of the young rather than type 2 diabetes.
The E224K mutation cosegregated with early-onset diabetes or impaired glucose tolerance in a large family, suggestive of the type 4 form of maturity-onset diabetes of the young rather than type 2 diabetes.
The E224K mutation cosegregated with early-onset diabetes or impaired glucose tolerance in a large family, suggestive of the type 4 form of maturity-onset diabetes of the young rather than type 2 diabetes.
The P239Q variant was identified in two families with early-onset diabetes including one with MODY3 (R272C of HNF1alpha) and in three families with late-onset Type II diabetes.
Neither the D76N nor the A140T segregated with diabetes, and their transcriptional activation of the human insulin promoter expressed in vitro was indistinguishable from that of the wild type (115 +/- 21% and 84 +/- 12% vs. 100%).