ABSTRACT
This study aimed to analyze the association between UBE2E2, G6PC2, PROX1, DUSP9, ADCY5 and APOC3 polymorphisms and the risk of metabolic syndrome (MetS) in Moroccan patients. The study was applied on 316 unrelated individuals from Morocco, 177 MetS patients and 139 controls. The metabolic syndrome was diagnosed according to the International Diabetes Federation (IDF) criteria. All subjects were genotyped for the following polymorphisms: rs7612463 (UBE2E2), rs560887 (G6PC2), rs340874 (PROX1), rs5945326 (DUSP9), rs11708067 (ADCY5) and rs5128 (APOC3) using TaqMan allelic discrimination assay and PCR-RFLP. The rs5128 (APOC3) and rs340874 (PROX1) polymorphisms were found to be significantly associated with susceptibility to MetS (P=0.003 and P=0.033, respectively), with odds ratios (ORs) of 4.39 (95% CI=1.66-11.56) and 2.81 (95% CI=1.09-7.27), respectively. Two variants presented a tendency to be protector factors against MetS risk: rs5945326 in DUSP9 gene (OR=0.32; 95% CI=0.17-0.62; =0.001) and rs11708067 in ADCY5 gene (OR=0.51; 95% CI=0.28-0.95; P=0.034). No association was detected between rs7612463 (UBE2E2) and rs560887 (G6PC2) SNPs and MetS increased risk. This study suggests a potential role of rs5128, rs340874, rs5945326 and rs11708067 variants in MetS susceptibility in the Moroccan population.
Subject(s)
Metabolic Syndrome/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Case-Control Studies , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Humans , Male , Metabolic Syndrome/epidemiology , Middle Aged , Morocco/epidemiologyABSTRACT
BACKGROUND: Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal dominant inherited cancer syndrome that affects multiple tissues derived from the neural crest. Inheritance of MTC is related to the presence of specific mutations in the RET proto-oncogene. Almost all mutations in MEN 2A involve one of the cysteines in the extracellular domain of the RET receptor. AIMS: The objective of the present study was the biochemical and molecular characterization of the first Moroccan clinically established MEN 2A patient and at-risk family members. SETTINGS AND DESIGN: This is a study on a family presented with MTC referred to our institute in 2004. MATERIALS AND METHODS: Peripheral blood leukocyte DNA samples were isolated and amplified by polymerase chain reaction followed by restriction enzyme analysis and DNA sequencing. RESULTS: We identified a heterozygous germ line missense mutation at codon 634 of exon 11 in the RET gene that causes a cysteine to arginine amino acid substitution in the DNA of the proband; this mutation was not found in the DNA of the parents or relatives. CONCLUSIONS: The detection of mutated MEN 2A gene carriers enables us to differentiate high-risk members from those who bear the wild-type gene. Occasionally, application of RET proto-oncogene testing may lead to the detection of unexpected de novo mutation that could be transmitted to children.
Subject(s)
Carcinoma, Medullary/genetics , Proto-Oncogene Proteins c-ret/genetics , Thyroid Neoplasms/genetics , Adolescent , Adrenal Gland Neoplasms/genetics , Carcinoma, Medullary/surgery , DNA Mutational Analysis , Family , Female , Humans , Morocco , Multiple Endocrine Neoplasia Type 2a/complications , Multiple Endocrine Neoplasia Type 2a/genetics , Pedigree , Pheochromocytoma/genetics , Proto-Oncogene Mas , Thyroid Neoplasms/surgery , ThyroidectomyABSTRACT
BACKGROUND: Calcitonin is the most sensitive and specific marker for medullary thyroid carcinoma (MTC). AIMS: The aim of this study was to emphasize the role and the limits of plasma basal calcitonin (bCT) measurement in the management of Moroccan MTC patients and their relatives. SETTINGS AND DESIGN: This is a retrospective study on 6 MTC patients referred to our institute from January 1996 to December 2004. MATERIALS AND METHODS: Serum bCT levels were measured in 36 individuals comprising six known MTC cases, 18 relatives and 12 healthy volunteers, using two-sites immunoradiometric assay method. Five of MTC patients have been followed from 12 to 96 months after surgery. STATISTICAL ANALYSIS USED: Calculations were performed using SPSS 10.0 program. Data comparison was done by Student's t -test. RESULTS: The circulating preoperative bCT concentrations were elevated for all MTC patients (range, 44,8 -2055 pg/ml, normal <10). Recent postoperative bCT determinations varied from 24.4 to 1972 pg/ml in four patients. In one patient, the bCT value decreased to an undetectable level during a follow-up of 12 months. The mean bCT level of relatives was 4.90 +/- 3.54 pg/ml; two patients had slightly elevated bCT. Five (42%) healthy volunteers had undetectable bCT levels and all had less than 10 pg/ml; the mean bCT value was 3.06 +/- 2.51 pg/ml. CONCLUSIONS: Routine plasma bCT measurement still has an important place in the preoperative diagnosis and follow-up treatment of MTC.
