Hashim_2001_Diabetologia_44_2227

AIMS/HYPOTHESIS To determine the association of three genes associated with Alzheimer's disease butyrylcholinesterase BcHE on chromosome 3 q alpha2 macroglobulin alpha2M on chromosome 12 p and apolipoprotein E ApoE on chromosome 19 q with Type II non-insulin-dependent diabetes mellitus METHODS Frequencies of BcHE K variant alpha2M insertion and/or deletion polymorphism the ApoE common polymorphisms and promoter variants at ApoE-491 and 291 were examined by fluorescent RFLP in DNA from 276 United Kingdom Prospective Diabetes Study Type II diabetic subjects and 351 non-diabetic subjects from the Diabetes In Families study Genetic data in diabetic subjects was analysed in relation to clinical characteristics and islet function as assessed by the requirement for insulin therapy 6 years after randomisation RESULTS The BcHE K variant allele was more common among Type II diabetic subjects D than non-diabetic subjects ND 22.8 D vs 15.8 ND p 0.00 017 Subjects homozygous for the variant were more frequent in the diabetic group 5.8 D vs 2.6 ND p 0.00 056 The K variant allele frequency was not associated with a requirement for insulin therapy 29.0 insulin-requiring vs 21.8 non-insulin-requiring p 0.121 There were no associations of alpha2M and ApoE polymorphisms or ApoE promoter variants with clinical characteristics or insulin requirement in diabetic subjects There were differences in total cholesterol p 0.0005 and LDL-cholesterol p 0.0009 among non-diabetic subjects in relation to ApoE-491 genotypes CONCLUSION/INTERPRETATION The association of the BcHE gene 3q26 with Type II diabetes could be related to an identified susceptibility locus on chromosome 3q27 but appears to be independent of islet function The absence of diabetes-specific associations with alpha2M ApoE or ApoE promoter variants suggest that these are not important in the onset of hyperglycaemia Diabetologia 2001 44 2227-2230