***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE : To estimate the possibility of long-term effects of sub clinical thyroid dysfunction on  hypertension  and other cardiovascular-related conditions during pregnancy . METHODS : This is a secondary analysis of a prospect i ve prenatal population -based study in which  serum thyroid-function analytes  were measured from November 2000 through April 2003 . Women with evidence of overt thyroid disease were excluded . The remaining women were classified as being euthyroid , having sub clinical hyperthyroid , or having sub clinical hypothyroid , and the frequency of pregnancy-associated hypertensive disorders was compared between these groups . RESULTS : Pregnancy outcomes in 24,883 women were analyzed for pregnancy hypertension  , classified as gestational hypertension , mild preeclampsia , or severe preeclampsia . The incidence of hypertensive disorders were compared between the three cohorts . The overall incidences of hypertension in pregnancy were 6.2 % , 8.5 % , and 10.9 % in the sub clinical hyperthyroid , euthyroid , and sub clinical hypothyroid groups , respectively , and were found to be significant when unadjusted ( P=.016 ) . After adjusting for confounding factors , there was a significant association between sub clinical hypothyroidism and severe preeclampsia ( adjusted odds ratio 1.6 , 95 % confidence interval 1.1–2.4 ; P=.03 ) . CONCLUSION : Women with sub clinical hypothyroidism identified during pregnancy have an increased risk for severe preeclampsia when compared with euthyroid women . LEVEL OF EVIDENCE : New Zeal and has one of the highest incidence rates of Crohn ’s Disease ( CD ) , whilst the serum selenium status of New Zeal and ers is amongst the lowest in the world . A prospect i ve case-control study in Auckl and , New Zeal and considered serum selenium as a potential CD risk factor . Serum selenium levels were significantly lower in CD patients compared to controls ( 101.8 ± 1.02 vs. 111.1 ± 1.01 ng/mL ) ( p = 5.91 × 10−8 ) . Recent detailed studies in the United Kingdom have suggested an optimal serum level around 122 ng/mL , making the average CD patient in New Zeal and selenium deficient . Of the 29 single nucleotide polymorphisms ( SNPs ) tested , 13 were found to significantly interact with serum selenium  on CD . After adjustment for multiple testing , a significant interaction with serum selenium on CD was found for three SNPs , namely rs17529609 and rs7901303 in the gene SEPHS1 , and rs1553153 in the gene SEPSECS . These three SNPs have not been reported elsewhere as being significantly associated with selenium or CD . It is unclear as to whether  lower selenium levels are a cause or an effect of the disease Type II deiodinase ( D2 ) is important in the regulation of local thyroid hormone bioactivity in certain tissues . D2 in skeletal muscle may also play a role in serum triiodothyronine ( T(3 ) ) production . In this study , we identified a polymorphism in the 5'-UTR of the D2 gene ( D2-ORFa-Gly3Asp ) . We investigated the association of D2-ORFa-Gly3Asp , and of the previously identified D2-Thr92Ala polymorphism , with serum iodothyronine levels . D2-ORFa-Gly3Asp was identified by sequencing the 5'-UTR of 15 r and omly selected individuals . Genotypes for D2-ORFa-Gly3Asp were determined in 156 healthy blood donors ( age 46.3 + /- 12.2 yr ) and 349 ambulant elderly men ( age 77.7 + /- 3.5 yr ) and related to serum iodothyronine and TSH levels .  D2-ORFa-Asp(3 ) had an allele frequency of 33.9 % in blood bank donors and was associated with serum thyroxine ( T(4 ) ; Gly/Gly vs. Gly/Asp vs. Asp/Asp = 7.06 + /- 0.14 vs. 6.74 + /- 0.15 vs. 6.29 + /- 0.27 microg/dl , P = 0.01 ) , free T(4 ) ( 1.22 + /- 0.02 vs. 1.16 + /- 0.02 vs. 1.06 + /- 0.04 ng/dl , P = 0.001 ) , reverse T(3 ) ( P = 0.01 ) , and T(3)/T(4 ) ratio ( P = 0.002 ) in a dose-dependent manner , but not with serum T(3 ) ( P = 0.59 ) . In elderly men , D2-ORFa-Asp(3 ) had a similar frequency but was not associated with serum iodothyronine levels . This new polymorphism in the 5'-UTR of D2 is associated with iodothyronine levels in blood donors but not in elderly men . We hypothesize that this might be explained by the decline in skeletal muscle size during aging , result ing in a relative decrease in the contribution of D2 to serum T(3 ) production Single nucleotide polymorphisms ( SNPs ) in genes involved in thyroid hormone metabolism may affect thyroid hormone bioactivity . We investigated the occurrence and possible effects of SNPs in the deiodinases ( D1-D3 ) , the TSH receptor ( TSHR ) , and the T(3 ) receptor beta ( TR beta ) genes . SNPs were identified in public data bases or by sequencing of genomic DNA from 15 r and omly selected subjects ( 30 alleles ) . Genotypes for the identified SNPs were determined in 156 healthy blood donors and related to plasma T(4 ) , free T(4 ) , T(3 ) , rT(3 ) , and TSH levels . Eight SNPs of interest were identified , four of which had not yet been published . Three are located in the 3'-untranslated region : D1a-C/T ( allele frequencies , C = 66 % , T = 34 % ) , D1b-A/G ( A = 89.7 % , G = 10.3 % ) , and D3-T/G ( T = 85.5 % , G = 14.2 % ) . Four are missense SNPs : D2-A/G ( Thr92Ala , Thr = 61.2 % , Ala = 38.8 % ) , TSHRa-G/C ( Asp36His , Asp = 99.4 % , His = 0.6 % ) , TSHRb-C/A ( Pro52Thr , Pro = 94.2 % , Thr = 5.8 % ) , and TSHRc-C/G ( Asp727Glu , Asp = 90.7 % , Glu = 9.3 % ) . One is a silent SNP : TR beta-T/C ( T = 96.8 % , C = 3.2 % ) . D1a-T was associated in a dose-dependent manner with a higher plasma rT(3 ) [ CC , 0.29 + /- 0.01 ; CT , 0.32 + /- 0.01 ; and TT , 0.34 + /- 0.02 nmol/liter ( mean + /- SE ) ; P = 0.017 ] , a higher plasma rT(3)/T(4 ) ( P = 0.01 ) , and a lower T(3)/rT(3 ) ( P = 0.003 ) ratio . The D1b-G allele was associated with lower plasma rT(3)/T(4 ) ( P = 0.024 ) and with higher T(3)/rT(3 ) ( P = 0.08 ) ratios . TSHRc-G was associated with a lower plasma TSH ( CC , 1.38 + /- 0.07 , vs. GC , 1.06 + /- 0.14 mU/liter ; P = 0.04 ) , and with lower plasma TSH/free T(4 ) ( P = 0.06 ) , TSH/T(3 ) ( P = 0.06 ) , and TSH/T(4 ) ( P = 0.08 ) ratios . No associations with TSH and iodothyronine levels were found for the other SNPs . We have analyzed eight SNPs in five thyroid hormone pathway genes and found significant associations of three SNPs in two genes ( D1 , TSHR ) with plasma TSH or iodothyronine levels in a normal population BACKGROUND The common Thr92Ala D2 polymorphism has been associated with changes in pituitary-thyroid axis homeostasis , but published results are conflicting . To investigate the effects of the Thr92Ala polymorphism on intrathyroidal thyroxine ( T4 ) to triiodothyronine ( T3 ) conversion , we design ed prospect i ve pharmacogenomic intervention aim ed to detect differences in T3 levels after thyrotropin (TSH)-releasing hormone (TRH)-mediated TSH stimulation of the thyroid gl and . METHODS Eighty-three healthy volunteers were screened and genotyped for the  Thr92Ala polymorphism .  Fifteen volunteers of each genotype ( Thr/Thr , Thr/Ala , and Ala/Ala ) underwent a 500 mcg intravenous TRH stimulation test with serial measurements of serum total T3 ( TT3 ) , free T4 , and TSH over 180 minutes . RESULTS No differences in baseline thyroid hormone levels were seen among the study groups . Compared to the Thr/Thr group , the Ala/Ala group showed a significantly lower TRH-stimulated increase in serum TT3 at 60 minutes ( 12.07 ± 2.67 vs. 21.07 ± 2.86 ng/dL , p = 0.029 ) . Thr/Ala subjects showed an intermediate response . Compared to Thr/Thr subjects , the Ala/Ala group showed a blunted rate of rise in serum TT3 as measured by mean time to 50 % maximum delta serum TT3 ( 88.42 ± 6.84 vs. 69.56 ± 6.06 minutes , p = 0.028 ) . Subjects attained similar maximal ( 180 minutes ) TRH-stimulated TT3 levels . TRH-stimulated TSH and free T4 levels were not significantly different among the three genotype groups . CONCLUSIONS The commonly occurring Thr92Ala D2 variant is associated with a decreased rate of acute TSH-stimulated T3 release from the thyroid consistent with a decrease in intrathyroidal deiodination . These data provide a proof of concept that the Thr92Ala polymorphism is associated with subtle changes in thyroid hormone homeostasis Objective The type 2 deiodinase (D2)‐Thr92Ala polymorphism has been associated with decreased D2 activity in some in vitro experiments but not in others . So far no association between the D2‐Thr92Ala polymorphism  and serum thyroid hormone levels has been observed in humans , but in a recent study in athyroid patients , it was suggested that patients homozygous for the Ala92 allele needed higher T4 doses to achieve TSH suppression 
    Output:
    
Deiodinase type 1 ( D1 ) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters , IGF1 production , and risk for depression .
D2 variants correlate with thyroid hormone levels , insulin resistance , bipolar mood disorder , psychological well-being , mental retardation , hypertension , and risk for osteoarthritis .
D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters .
One D3 polymorphism was associated with risk for osteoarthritis .
Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels .
Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions .