ABSTRACT: Polymorphisms of the gene encoding adiponectin (ADIPOQ) have previously been associated with type 2 diabetes in Europid and Japanese subjects, but not in Pima Indians. The aim of this study was to determine the contribution made by ADIPOQ gene variants to glycaemic status in southern Chinese individuals.
Sixty unrelated subjects were screened for single-nucleotide polymorphisms (SNPs) in the ADIPOQ gene by direct sequencing. The association of tagging SNPs with the outcome of glycaemic status in 262 subjects with impaired glucose tolerance (IGT) was examined in a 5-year prospective study.
We identified 15 polymorphisms in the ADIPOQ gene, ten of them constituting the tagging SNPs. At 5 years, 39.7% of the subjects with IGT had regressed to NGT, 41.2% had persistent IGT or impaired fasting glucose and 19.1% had developed diabetes. Only the T45G polymorphism was associated with persistent hyperglycaemia at 5 years (p=0.001). Haplotypes formed by the addition of other SNPs, as haplotype blocks or pairs, did not confer greater association than T45G alone. On logistic regression analysis, T45G independently predicted persistent hyperglycaemia at 5 years (OR=2.25, 95% CI 1.29-3.95, G carriers vs TT; p=0.005). It also predicted persistent hyperglycaemia in a nested case-control study involving 158 sex- and age-matched controls with persistent NGT (p=0.012, adjusted for BMI), and that of diabetes or glycaemia progression (p<0.05) in a meta-analysis that also included two published studies in Europid subjects.
Our findings support a significant role of this common ADIPOQ gene polymorphism in predicting glycaemic status in southern Chinese people.
Diabetologia 09/2006; 49(8):1806-15. · 6.81 Impact Factor
ABSTRACT: Multiple endocrine neoplasia type 1 (MEN1) is characterized by a triad of neoplasia affecting the parathyroid glands, enteropancreatic endocrine tissue and the anterior pituitary gland.
In order to define the prevalence of MEN1 germ-line mutations in Southern Chinese patients with MEN1 syndrome, we performed direct sequencing of the entire open reading frame of the MEN1 gene for 12 index patients and their first-degree relatives.
Six patients had familial MEN1 syndrome and six had apparently sporadic disease. Nine different germ-line mutations at the MEN1 gene were identified, including three novel mutations [248-249delTT in exon 2, K559X(AAG --> TAG) in exon 10 and IVS 2nt + 2(G --> T) in intron 2]. All patients with familial MEN1 syndrome were heterozygous carriers of a germ-line mutation and MEN1-related disorders were only evident in their first-degree relatives who also carried the mutation. All patients with an enteropancreatic lesion were mutation carriers and the absence of mutation in three apparently sporadic MEN1 patients with only hyperparathyroidism and pituitary microadenoma might represent the presence of MEN1 phenocopy.
The finding of MEN1 germ-line mutation in all patients with familial MEN1 syndrome suggests that genetic screening should be useful in our population to identify affected individuals within a kindred and allow early detection of MEN1-related tumours.
Clinical Endocrinology 07/2003; 59(1):129-35. · 3.17 Impact Factor
ABSTRACT: Maturity-onset diabetes of the young is an autosomal dominant form of diabetes characterised by an early age of onset (usually <25 years). We investigated the prevalence and trans-activating activity of hepatocyte nuclear factor (HNF) -1 alpha mutations in southern Chinese families with MODY.
We screened for mutations in the HNF-1 alpha gene in 50 unrelated southern Chinese families, which fulfilled the minimum criteria for MODY. Functional properties of the mutant proteins were investigated using site-directed mutagenesis and luciferase reporter assay.
Five of the 50 (10%) families were found to have mutations in the coding region, including a new nonsense mutation Q176X and four reported mutations (frameshift mutation P379fsdelCT, nonsense mutation R171X, missense mutations G20R and P112L). These mutations had decreased trans-activating activity on the human insulin gene promoter. We also detected a new intronic sequence variation IVS7nt-6 G-->A, which co-segregated with diabetes. The intronic variation creates a potential splice acceptor site and might alter the splicing of the HNF-1 alpha mRNA.
Mutations in the HNF-1 alpha gene seem to be an important cause of MODY in southern Chinese. The mutations could affect normal islet function by altering the expression of target genes.
Diabetologia 05/2002; 45(5):744-6. · 6.81 Impact Factor