PMID- 22142372
OWN - NLM
STAT- MEDLINE
DCOM- 20120508
LR  - 20231213
IS  - 1557-9077 (Electronic)
IS  - 1050-7256 (Print)
IS  - 1050-7256 (Linking)
VI  - 22
IP  - 1
DP  - 2012 Jan
TI  - Association analyses of variants in the DIO2 gene with early-onset type 2 
      diabetes mellitus in Pima Indians.
PG  - 80-7
LID - 10.1089/thy.2010.0455 [doi]
AB  - BACKGROUND: The type 2 deiodinase gene (DIO2) encodes a deiodinase that converts 
      the thyroid prohormone, thyroxine, to the biologically active triiodothyronine. 
      Thyroid hormones regulate energy balance and may also influence glucose 
      metabolism. Therefore, we hypothesized that variations in DIO2 could contribute 
      to obesity or type 2 diabetes mellitus (T2DM) in Pima Indians. METHODS: 
      Sequencing of the DIO2 gene in DNA from 83 Pima Indians identified 12 
      single-nucleotide polymorphisms (SNPs). Several of these SNPs were in perfect 
      genotypic concordance among the 83 samples that were sequenced, and all 12 could 
      be divided into five linkage disequilibrium groups. One representative SNP from 
      each group (Thr92Ala, rs225011, rs225015, rs6574549, and a rare 5' flanking SNP) 
      was selected for further genotyping for association analyses. In this study, the 
      five selected variants in DIO2, as described above, were genotyped in three 
      groups of Pima Indians: (i) a case (n=150)/control (n=150) group for early-onset 
      T2DM (onset age <25 years); (ii) a case (n=362)/control (n=127) group for 
      obesity; (iii) a large (n=1,311, cases n=810/controls n=501) family-based group, 
      of which 256 nondiabetic subjects had undergone detailed metabolic phenotyping. 
      RESULTS: The Thr92Ala variant common in Pima Indians, rs225011, and rs225015 were 
      modestly associated with early-onset T2DM (p=0.01-0.04) in the case-control 
      study, but were not associated with obesity in the obesity case-control study, 
      nor associated with T2DM (at any age) or body-mass index (BMI; as a quantitative 
      trait) in the family-based analysis. Thr92Ala, rs225011, rs225015, and rs6574549 
      were also nominally associated with hepatic glucose output (p=0.02). rs6574549 
      was associated with fasting insulin (p=0.02), insulin action (p=0.04), and energy 
      expenditure (p=0.02). None of these nominal associations remained statistically 
      significant after corrections for multiple testing. CONCLUSIONS: We propose that 
      variation in DIO2 may have a subtle role in altering metabolic processes that 
      lead to early-onset T2DM, but this gene does not have a large impact on T2DM at 
      older ages, nor does DIO2 influence BMI in the Pima Indian population.
FAU - Nair, Saraswathy
AU  - Nair S
AD  - Diabetes Molecular Genetics Section, Phoenix Epidemiology and Clinical Research 
      Branch, National Institute of Diabetes and Digestive and Kidney Diseases, 
      National Institutes of Health, Phoenix, Arizona, USA. saraswathy.nair@utb.edu
FAU - Muller, Yunhua Li
AU  - Muller YL
FAU - Ortega, Emilio
AU  - Ortega E
FAU - Kobes, Sayuko
AU  - Kobes S
FAU - Bogardus, Clifton
AU  - Bogardus C
FAU - Baier, Leslie J
AU  - Baier LJ
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20111205
PL  - United States
TA  - Thyroid
JT  - Thyroid : official journal of the American Thyroid Association
JID - 9104317
RN  - EC 1.11.1.8 (Iodide Peroxidase)
SB  - IM
MH  - Adult
MH  - Age of Onset
MH  - Body Mass Index
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/*ethnology/*genetics
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Indians, North American
MH  - Iodide Peroxidase/*genetics
MH  - Linkage Disequilibrium
MH  - Obesity, Morbid/*genetics
MH  - Polymorphism, Single Nucleotide
MH  - Iodothyronine Deiodinase Type II
PMC - PMC3247704
EDAT- 2011/12/07 06:00
MHDA- 2012/05/09 06:00
PMCR- 2013/01/01
CRDT- 2011/12/07 06:00
PHST- 2011/12/07 06:00 [entrez]
PHST- 2011/12/07 06:00 [pubmed]
PHST- 2012/05/09 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 10.1089/thy.2010.0455 [pii]
AID - 10.1089/thy.2010.0455 [doi]
PST - ppublish
SO  - Thyroid. 2012 Jan;22(1):80-7. doi: 10.1089/thy.2010.0455. Epub 2011 Dec 5.