Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the polyglandular autoimmune syndrome type II.
BACKGROUND
Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from beta-cell autoimmunity.


METHODS
We investigated the role of the -2221Msp(C/T) and -23HphI(A/T) polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317), Addison's disease (AD, n = 107) or Hashimoto's thyroiditis (HT, n = 61)], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62) as well as in healthy controls (HC, n = 275).


RESULTS
T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T) and "AA" -23HphI(A/T) polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 x 10-8, respectively). The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC.


CONCLUSIONS
We demonstrate that the allele "C" of the -2221Msp(C/T) and "A" -23HphI(A/T) insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.
Ramos-Lopez
Elizabeth
E
Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, University Hospital Frankfurt, Frankfurt am Main, Germany. elizabeth.ramos-lopez@kgu.de
Lange
Britta
B
Kahles
Heinrich
H
Willenberg
Holger S
HS
Meyer
Gesine
G
Penna-Martinez
Marissa
M
Reisch
Nicole
N
Hahner
Stefanie
S
Seissler
Jürgen
J
Badenhoop
Klaus
K
D000224:Addison Disease / Q000150:complications / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics*; D005838:Genotype; D006111:Graves Disease / Q000150:complications / Q000235:genetics; D050031:Hashimoto Disease / Q000150:complications / Q000235:genetics; D006801:Humans; D007223:Infant; D007328:Insulin / Q000235:genetics*; D008875:Middle Aged; D018598:Minisatellite Repeats; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D007328:Insulin