title: Polymorphism in intron 2 of islet amyloid polypeptide gene is associated with lower low-density lipoprotein cholesterol in nondiabetic subjects and in type 2 diabetic patients.
abstract: The aim of this study was to investigate the presence of mutations in the islet amyloid polypeptide (IAPP) gene in a Spanish population with type 2 diabetes and gestational diabetes mellitus (GDM). Using polymerase chain reaction single-stranded conformation polymorphism, we examined the coding region and the 5'-untranslated region (UTR) of the IAPP gene in 177 unrelated type 2 diabetic patients, 110 healthy control subjects, 38 women with GDM, and 38 gestational control subjects. Mutations were confirmed by DNA sequencing. A heterozygous C-to-A nucleotide substitution at +79 bp in intron 2 of the IAPP gene was detected. The frequencies of the +79-bp polymorphism (A allele) were 6.8% in type 2 diabetic patients, 7.7% in nondiabetic control subjects, 11.8% in women with GDM, and 9.2% in gestational control subjects. No AA genotypes were detected. Nondiabetic subjects and patients with type 2 diabetes bearing the CA genotype had lower low-density lipoprotein (LDL) cholesterol levels than subjects bearing wild genotype. Multivariate logistic regression analysis showed an independent association (p < 0.001; odds ratio: 0.33; 95% confidence interval: 0.17-0.63). We did not detect any sequence variant within exons 1 or 2. One diabetic patient was heterozygous for a silent mutation at codon 31 of exon 3 (Asn31 AAC --> AAT). Our findings indicate that the presence of the +79-bp polymorphism of the IAPP gene in nondiabetic subjects and in patients with type 2 diabetes is associated with lower levels of LDL cholesterol. Furthermore, abnormalities of the coding regions or the 5'-UTR of the IAPP gene are not associated with type 2 diabetes or GDM in the Spanish population.
authors.affiliation: Diabetes Institute, Fundació Sardà Farriol, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Rojas
authors.forename: R
authors.initials: R
authors.lastname: Gomis
authors.forename: E
authors.initials: E
authors.lastname: Casals
authors.forename: L I
authors.initials: LI
authors.lastname: Quintó
authors.forename: C
authors.initials: C
authors.lastname: Franco
authors.forename: A
authors.initials: A
authors.lastname: Novials
mesh_terms: D000368:Aged; D000682:Amyloid / Q000235:genetics*; D016022:Case-Control Studies; D008078:Cholesterol, LDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007438:Introns; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D000682:Amyloid; D008078:Cholesterol, LDL; D058228:Islet Amyloid Polypeptide