Islet amyloid polypeptide gene promoter polymorphisms are not associated with Type 2 diabetes or with the Eseverity of islet amyloidosis

The over-expression of the islet amyloid polypeptide (IAPP) gene could be a causal factor for islet amyloidosis and beta-ccll destruction in Type 2 diabetes (T2DM). An LAPP gene promoter polymorphism, LAPP-132G to A, has been associated with T2DM in Spain, To investigate this polymorphism in other cohorts and in relation to therapy, DNA from 425 T2DM and 279 unrelated, non-diabetic UK subjects (ND) and 102 T2DM and 80 ND Finnish subjects was examined. The relationship of amyloid severity (percent amyloid/islet) to prevalence (number of islets affected) and the association of LAPP-132G/A with amyloid was determined in post-mortem pancreas from 38 T2DM subjects. The -132G/A was not associated with T2DM in the UK cohorts (4.51% T2DM: 3.2% ND) or associated with requirement for insulin therapy by 6 years. The mutation was and undetected in the Finnish samples but a new variant, -166T/C. was identified in 2 Finnish T2DM subjects. -132G/A was found in 2/38 diabetic, amyloid-containing and 3/19 ND, amyloid-free subjects. The islet amyloid severity was linearly correlated with the prevalence in T2DM. The LAPP-132G/A promoter polymorphism is not associated with T2DM, a requirement for insulin therapy or with the degree of islet amyloidosis in cohorts from the UK or Finland, (c) 2005 Elsevier B.V. All rights reserved.