Pancreatic hemi-agenesis in MEN1: A clinical report.

We first describe a patient with multiple endocrine neoplasia type 1 (MEN1) and dorsal pancreatic hemi-agenesis. Previously, pancreas divisum has been reported in MEN1. Recent data in mice have elucidated the molecular mechanisms of pancreatic endoderm specification. Disinhibition of hedgehog signaling appears to be important in how Gata4 and Gata6 variants cause pancreatic agenesis. Disinhibition of hedgehog signaling has also been observed in Men1 knockout pancreatic islets. Although we cannot exclude a spurious association between dorsal pancreatic hemi-agenesis and MEN1 in our patient, we argue that developmental abnormalities of the pancreas may have to be considered as possibly related to the MEN1 phenotype.

Cardiovascular risk assessment in hypertensive patients: major discrepancy according to ESH and SCORE strategies.

BACKGROUND: The European Society of Hypertension (ESH) guidelines recommend two possible strategies for the assessment of cardiovascular risk (CVR) in essential hypertensive (HT) patients: categorical tables and SCORE risk charts. However, the outcome of these methods has not been compared. OBJECTIVE AND METHODS: We assessed CVR according to ESH and SCORE risk charts adapted to use in Belgium in 106 HT patients (mean age: 52.4 +/- 12.9 years, male/female ratio: 46/60) without diabetes or other associated clinical conditions. RESULTS: The distribution of low, moderate, high and very high added risk was strikingly different (kappa coefficient = 0.08) according to ESH categorical tables (n = 1, 24, 24, 57) and SCORE risk charts (n = 60, 12, 10, 24). Furthermore, compared with ESH, CVR class according to SCORE was lower in the majority of patients (n = 72, 68%) while it was similar in 23 (22%) and higher in 11 patients (10%). Patients for whom risk was lower by SCORE compared to ESH differed from the others by age (46.7 +/- 10.0 versus 64.6 +/- 9.2, P < 10) and proportion of females (71 versus 26%, P < 10). CONCLUSIONS: In this series of patients with mainly moderate or severe hypertension, the distribution of cardiovascular risk was strikingly different according to ESH categorical tables and SCORE risk charts. This might be explained in part by the lower weight attributed to blood pressure in risk assessment, especially in young female subjects. If confirmed, these results should prompt the performance of a prospective study to assess which strategy most accurately predicts CVR in hypertensive patients.

Influence of the endothelial nitric oxide synthase gene on conventional and ambulatory blood pressure: sib-pair analysis and haplotype study.

BACKGROUND: Nitric oxide is involved in the regulation of vascular basal tone and blood pressure. Polymorphisms of NOS3, the gene that codes for endothelial nitric oxide synthase, have been associated with essential hypertension. OBJECTIVE: To look for linkage and association of three di-allelic polymorphisms (Glu298Asp, intron 4 VNTR and T-786C) and the intron 13 CA-repeat of NOS3 with blood pressure as a continuous trait. METHODS: Genotyping was performed in 110 dizygotic white twin pairs from Flanders, Belgium. The influence of NOS3 polymorphisms on conventional and ambulatory blood pressure was assessed by sib-pair analysis and haplotype association analysis. RESULTS: Genotype frequencies were similar to those previously reported in white populations. Sib-pair analysis did not show a significant influence of either polymorphism on blood pressure. Haplotype analysis disclosed a significant association between NOS3 haplotypes and daytime ambulatory diastolic (P = 0.02) and systolic (P < 0.0001) blood pressure, the latter remaining significant after multiple testing was taken into account (P = 0.032). The association between daytime ambulatory systolic blood pressure and NOS3 haplotypes was mainly attributable to four haplotypes accounting for 11.9% of all represented haplotypes. CONCLUSION: We show for the first time a highly significant association of ambulatory blood pressure with NOS3 haplotypes in well-characterized white individuals from Flanders. These results pave the way for studies looking for the influence of NOS3 on blood pressure in high-risk subsets such as diabetic or hypertensive patients. They indicate the importance of ambulatory blood pressure and haplotype analysis in revealing the moderate effect of polymorphisms on blood pressure.