Androgen receptor gene exon 1 CAG repeat polymorphism in Finnish patients with childhood-onset type 1 diabetes.
OBJECTIVE
Animal models suggest that androgen receptor gene polymorphisms might affect disease predisposition in human immune-mediated diabetes. The aim of this study was to investigate the effect of the human androgen receptor gene exon 1 CAG repeat polymorphisms on type 1 diabetes (T1D) susceptibility.


METHODS
A combined strategy of case-control and family-based approaches was used. Affected sibling pair families (n=120), nuclear families (n=645) and cohorts of sporadic cases (n=208) and controls (n=1381) were genotyped for androgen receptor gene exon 1 CAG repeat polymorphism. An automated fluorescence-based DNA fragment-sizing method was used.


RESULTS
The distribution of CAG repeat alleles did not differ significantly between patients and controls. However, short repeat alleles (7-14) were more prevalent among cases in girls compared with controls (8.77% vs 5.91%; P=0.03). Long repeat alleles (19-28) were less frequent among HLA DR3-positive diseased boys than in DR3-positive control boys (32.6% vs 40.6%; P=0.011). The differences were not significant after adjustment for multiple comparisons. Transmission of CAG repeat alleles was not different from expected in the total material. However, transmissions to girls deviated from the expected value significantly (extended transmission disequilibrium test (ETDT) 37.82; P=0.0016). A decreased transmission of the alleles with 13, 20 and 26 repeats to girls was observed (T%0, P=0.046; T%25.5, P=0.0003, T%0, P=0.025).


CONCLUSIONS
The results do not support a common role for the androgen receptor gene exon 1 CAG repeat in T1D susceptibility; however, an effect of a disease variant in linkage disequilibrium could be detected.
Gombos
Zsofia
Z
JDRF Centre for Prevention of Type 1 Diabetes in Finland, Turku, Finland. zsogom@utu.fi
Hermann
Robert
R
Veijola
Riitta
R
Knip
Mikael
M
Simell
Olli
O
Pöllänen
Pasi
P
Ilonen
Jorma
J
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D015803:HLA-DR3 Antigen / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics*; D012727:Sex Characteristics; D018911:Trinucleotide Repeats / Q000235:genetics*
D015803:HLA-DR3 Antigen; D011944:Receptors, Androgen