Positive association of the DIO2 (deiodinase type 2) gene with mental retardation in the iodine-deficient areas of China.
BACKGROUND
Iodine deficiency is the commonest cause of preventable mental retardation (MR) worldwide. However, in iodine-deficient areas not everyone is affected and familial aggregation is common. This suggests that genetic factors may also contribute. Thyroid hormone (TH) plays an important role in fetal and early postnatal brain development. The pro-hormone T4 (3,3',5,5'-triiodothyronine) is converted in the brain to its active form, T3, or its inactive metabolite, reverse T3, mainly by the action of deiodinase type 2 (DIO2).


METHODS
To investigate the potential genetic contribution of the DIO2 gene, we performed a case-control association study using three common SNPs in the gene (rs225014, rs225012, and rs225010) that were in strong linkage disequilibrium with each other.


RESULTS
Single marker analysis showed a positive association of MR with rs225012 and rs225010. Particularly with rs255012 [corrected], CC [corrected] genotype frequency was significantly higher in MR cases than in controls (chi squared [corrected] = 9.18, p = 0.00246). When we compared the distributions of common haplotypes, we also found significant differences between mental retardation and controls in the haplotype combination of rs225012 and rs225010 (chi2 = 15.04, df 2, global p = 0.000549). This association remained significant after Bonferroni correction (p = 0.0016470).


CONCLUSIONS
We conclude that allelic variation in the DIO2 gene may affect the amount of T3 available and in an iodine-deficient environment may partly determine overall risk of MR.
Guo
T-W
TW
Institute for Nutritional Science, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Zhang
F-C
FC
Yang
M-S
MS
Gao
X-C
XC
Bian
L
L
Duan
S-W
SW
Zheng
Z-J
ZJ
Gao
J-J
JJ
Wang
H
H
Li
R-L
RL
Feng
G-Y
GY
St Clair
D
D
He
L
L
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000201:enzymology / Q000235:genetics*; D007453:Iodide Peroxidase / Q000235:genetics*; D007455:Iodine / Q000172:deficiency* / Q000378:metabolism; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014284:Triiodothyronine / Q000378:metabolism; D000097564:Iodothyronine Deiodinase Type II
D005819:Genetic Markers; D007453:Iodide Peroxidase; D007455:Iodine; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II