{"id":"https://openalex.org/W2015507181","doi":"https://doi.org/10.1210/jc.2009-0410","title":"For Some, l-Thyroxine Replacement Might Not Be Enough: A Genetic Rationale","display_name":"For Some, l-Thyroxine Replacement Might Not Be Enough: A Genetic Rationale","publication_year":2009,"publication_date":"2009-05-01","ids":{"openalex":"https://openalex.org/W2015507181","doi":"https://doi.org/10.1210/jc.2009-0410","mag":"2015507181","pmid":"https://pubmed.ncbi.nlm.nih.gov/19420275"},"language":"en","primary_location":{"id":"doi:10.1210/jc.2009-0410","doi":"https://doi.org/10.1210/jc.2009-0410","is_oa":false,"landing_page_url":"https://doi.org/10.1210/jc.2009-0410","pdf_url":null,"source":{"id":"https://openalex.org/S205775358","display_name":"The Journal of Clinical Endocrinology & Metabolism","issn_l":"0021-972X","issn":["0021-972X","1945-7197"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-b","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journal of Clinical Endocrinology &amp; Metabolism","raw_type":"journal-article"},"volume":null,"type":"review","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5007424632","display_name":"Brian W. Kim","orcid":"https://orcid.org/0000-0001-6540-1110","observed_orcids":["https://orcid.org/0000-0001-6540-1110"]},"institutions":[{"id":"https://openalex.org/I145608581","display_name":"University of Miami","ror":"https://ror.org/02dgjyy92","country_code":"US","type":"education","lineage":["https://openalex.org/I145608581"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Brian W. Kim","raw_affiliation_strings":["Division of Endocrinology, Diabetes, and Metabolism, Miller School of Medicine, University of Miami, Miami, Florida 33136"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Endocrinology, Diabetes, and Metabolism, Miller School of Medicine, University of Miami, Miami, Florida 33136","institution_ids":["https://openalex.org/I145608581"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5026395401","display_name":"Antonio Carlos Bianco","orcid":"https://orcid.org/0000-0001-7737-6813","observed_orcids":["https://orcid.org/0000-0001-7737-6813"]},"institutions":[{"id":"https://openalex.org/I145608581","display_name":"University of Miami","ror":"https://ror.org/02dgjyy92","country_code":"US","type":"education","lineage":["https://openalex.org/I145608581"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Antonio C. Bianco","raw_affiliation_strings":["Division of Endocrinology, Diabetes, and Metabolism, Miller School of Medicine, University of Miami, Miami, Florida 33136"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Endocrinology, Diabetes, and Metabolism, Miller School of Medicine, University of Miami, Miami, Florida 33136","institution_ids":["https://openalex.org/I145608581"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5007424632"],"corresponding_institution_ids":["https://openalex.org/I145608581"],"apc_list":{"value":3750,"currency":"USD","value_usd":3750},"apc_paid":null,"fwci":0.2339,"has_fulltext":false,"cited_by_count":18,"citation_normalized_percentile":{"value":0.19480519,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":97},"biblio":{"volume":"94","issue":"5","first_page":"1521","last_page":"1523"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10293","display_name":"Thyroid Disorders and Treatments","score":0.9980000257492065,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10293","display_name":"Thyroid Disorders and Treatments","score":0.9980000257492065,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10329","display_name":"Thyroid Cancer Diagnosis and Treatment","score":0.00039999998989515007,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11728","display_name":"Thyroid and Parathyroid Surgery","score":0.0003000000142492354,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/hypothyroidism","display_name":"hypothyroidism","score":0.8510000109672546},{"id":"https://openalex.org/keywords/type-2-deiodinase","display_name":"type 2 deiodinase","score":0.9070000052452087},{"id":"https://openalex.org/keywords/endoplasmic-reticulum","display_name":"endoplasmic reticulum","score":0.6639999747276306},{"id":"https://openalex.org/keywords/ubiquitination","display_name":"ubiquitination","score":0.6549999713897705}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3771597445011139},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.32465219497680664}],"mesh":[{"descriptor_ui":"D000097564","descriptor_name":"Iodothyronine Deiodinase Type II","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007037","descriptor_name":"Hypothyroidism","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D007037","descriptor_name":"Hypothyroidism","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D007453","descriptor_name":"Iodide Peroxidase","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D013974","descriptor_name":"Thyroxine","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D014284","descriptor_name":"Triiodothyronine","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D020249","descriptor_name":"Hormone Replacement Therapy","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1210/jc.2009-0410","doi":"https://doi.org/10.1210/jc.2009-0410","is_oa":false,"landing_page_url":"https://doi.org/10.1210/jc.2009-0410","pdf_url":null,"source":{"id":"https://openalex.org/S205775358","display_name":"The Journal of Clinical Endocrinology & Metabolism","issn_l":"0021-972X","issn":["0021-972X","1945-7197"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-b","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journal of Clinical Endocrinology &amp; Metabolism","raw_type":"journal-article"},{"id":"pmid:19420275","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/19420275","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journal of clinical endocrinology and metabolism","raw_type":"Comment"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.8560000061988831}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":36,"referenced_works":["https://openalex.org/W1965529563","https://openalex.org/W1975345061","https://openalex.org/W1984225489","https://openalex.org/W2008671217","https://openalex.org/W2011275871","https://openalex.org/W2015843695","https://openalex.org/W2020693150","https://openalex.org/W2024116370","https://openalex.org/W2024579535","https://openalex.org/W2024675721","https://openalex.org/W2028086494","https://openalex.org/W2035160565","https://openalex.org/W2045087560","https://openalex.org/W2048245477","https://openalex.org/W2051726957","https://openalex.org/W2054867435","https://openalex.org/W2055205764","https://openalex.org/W2057808752","https://openalex.org/W2059487357","https://openalex.org/W2081028309","https://openalex.org/W2100049277","https://openalex.org/W2101256122","https://openalex.org/W2104878795","https://openalex.org/W2110110130","https://openalex.org/W2112251493","https://openalex.org/W2126038578","https://openalex.org/W2127669361","https://openalex.org/W2127811896","https://openalex.org/W2130754426","https://openalex.org/W2134734149","https://openalex.org/W2142623819","https://openalex.org/W2160937120","https://openalex.org/W2166554867","https://openalex.org/W2168714702","https://openalex.org/W2169118951","https://openalex.org/W2170475099"],"related_works":["https://openalex.org/W2110647490","https://openalex.org/W2326793315","https://openalex.org/W2611024120","https://openalex.org/W2953987536","https://openalex.org/W4313226337","https://openalex.org/W2134856350","https://openalex.org/W3093657104","https://openalex.org/W2072445480","https://openalex.org/W2035564025","https://openalex.org/W2201239534"],"abstract_inverted_index":{"Although":[0,1206],"the":[1,16,59,62,86,89,98,124,155,159,163,184,194,205,212,222,234,258,319,327,332,348,357,399,441,470,477,480,487,495,512,529,555,573,593,600,616,633,656,690,695,728,732,751,763,766,782,787,801,817,823,830,854,868,879,933,947,961,986,991,998,1005,1014,1068,1071,1078,1094,1155,1160,1190,1201,1207,1219,1224,1232,1251,1257,1260,1272,1275,1320,1333,1353,1361,1369,1381,1384,1407,1410,1414,1426,1430,1435],"thyroid":[2,11,29,68,197,259,307,364,376,444,704,1083,1281],"gland":[3,224,260],"secretes":[4],"a":[5,113,152,176,181,189,202,278,284,403,567,607,685,747,773,835,858,873,973,1041,1124,1403],"very":[6],"small":[7],"amount":[8],"of":[9,61,72,88,158,166,196,204,249,302,318,329,339,359,375,383,422,443,479,511,515,536,540,548,577,635,678,689,692,734,784,822,837,860,927,988,1016,1077,1082,1126,1157,1223,1259,1274,1295,1300,1324,1332,1346,1387,1409,1429],"active":[10,1221],"hormone":[12,30,69,198,308,365,377,445,705,1084],"(triiodothyronine":[13],"or":[14,415,533,938,1174,1188,1363],"T3),":[15],"major":[17],"circulating":[18],"form":[19],"is":[20,25,244,296,335,345,467,492,521,559,596,668,698,796,806,902,911,916,944,981,1154,1186,1203,1209,1216,1228,1235,1317,1356,1399,1402],"thyroxine":[21],"(T4),":[22],"and":[23,94,106,225,351,396,545,643,650,819,915,936,956,1008,1040,1051,1136,1169,1182,1226,1239,1282,1374],"it":[24,228,295,660,723,737,1227],"widely":[26,560],"accepted":[27],"that":[28,66,128,242,430,618,665,741,765,829,886,1129,1250,1269,1366,1383],"replacement":[31,199,1085],"in":[32,183,201,221,233,270,326,347,356,392,424,433,438,456,554,572,580,589,610,673,694,700,710,746,750,776,786,800,808,816,853,904,913,921,940,990,1036,1121,1141,1218,1237,1241,1279,1302,1319,1337,1434],"patients":[33,129,1038,1158],"with":[34,40,401,1031,1097,1108,1115,1134,1159,1163,1395,1421],"hypothyroidism":[35],"can":[36,354,436],"be":[37,264,663,760,791,834,1328,1372,1425],"fully":[38],"accomplished":[39],"l-T4":[41,1017,1103],"monotherapy":[42,1420],"[see":[43,1139],"1995":[44],"American":[45],"Thyroid":[46],"Association":[47],"guidelines":[48],"(Ref.":[49],"1)].":[50],"The":[51,420,543,676,793,1058,1087,1440],"mechanistic":[52,687],"basis":[53],"for":[54,148,154,372,406,451,463,531,566,570,655,670,715,756,839,890,952,957,970,997,1195,1212,1330,1358],"this":[55,173,757,980,1181,1199,1423],"belief":[56],"stems":[57],"from":[58,144,175,211,257,459,727,762,1043,1151],"actions":[60,87],"iodothyronine":[63],"deiodinases,":[64],"enzymes":[65],"activate":[67],"by":[70,268,469,524,1060],"conversion":[71],"T4":[73,105,289,582,838],"to":[74,85,95,110,116,193,263,266,288,292,298,315,388,413,461,476,585,615,662,718,731,790,968,1019,1027,1033,1067,1123,1165,1172,1327,1342,1417,1444],"T3":[75,111,120,160,254,267,341,353,587,612,636,648,667,717,744,767,1167],"(or":[76],"inactivate":[77],"both":[78,103,551],"forms":[79],"via":[80,494,538],"further":[81],"deiodination)":[82],"(2).":[83,238],"Thanks":[84],"type":[90,99,195,1449],"2":[91,1450],"deiodinase":[92,101,1448,1451],"(D2)":[93],"some":[96,149,510,525,590],"extent":[97,617],"1":[100,1447],"(D1),":[102],"endogenous":[104,1364],"l-t4":[107,134,1116],"are":[108,550,640,707,846,1090,1391],"converted":[109,265],"at":[112,139,486,552,883,919],"rate":[114],"sufficient":[115],"maintain":[117],"normal":[118,340],"serum":[119],"concentration.":[121],"However,":[122,857,1024,1287],"despite":[123],"extensive":[125,645],"literature":[126,646,1069],"demonstrating":[127],"do":[130,623],"well":[131,641,1012,1106],"clinically":[132],"on":[133,637,878,1102,1110,1348,1393,1413],"monotherapy,":[135],"most":[136],"clinicians":[137],"have":[138,453,620,719,865,929,949,1001,1442],"least":[140],"anecdotally":[141],"seen":[142,200],"benefits":[143],"combined":[145,1418],"T3/T4":[146,293,1112],"therapy":[147,649,1035,1113],"patients,":[150],"prompting":[151],"search":[153],"biological":[156],"mechanism":[157,237,405],"requirement.":[161],"In":[162,1245],"current":[164,1436],"issue":[165],"JCEM,":[167],"Panicker":[168,1061,1142],"et":[169,1062,1143],"al.":[170,1063,1144],"(3)":[171,1064],"examine":[172],"question":[174,1149],"novel":[177,448],"perspective,":[178],"asking":[179],"whether":[180,1187],"polymorphism":[182,281,876,935,964,1007,1096,1191,1454],"Dio2":[185,279,855,1049],"gene":[186,280],"could":[187,282,759],"explain":[188,283],"differential":[190,285],"psychological":[191,1100],"response":[192,287,1032,1416],"subpopulation":[203],"Weston":[206],"Area":[207],"T4/T3":[208],"Study":[209],"(WATTS)":[210],"United":[213],"Kingdom":[214],"(3,":[215],"4).":[216],"D2":[217,243,269,303,311,323,344,370,395,423,434,452,465,490,519,541,549,558,571,603,693,697,804,841,943,963,989,1196,1243,1263,1296,1325,1359],"was":[218,965],"initially":[219],"characterized":[220,870],"pituitary":[223],"hypothalamus,":[226,803],"where":[227,557,942],"plays":[229,772],"an":[230,246,644,679,888,982,1029,1091,1336],"important":[231,247,669,1329],"role":[232,569,691,775,987],"TSH/TRH":[235],"feedback":[236,658],"Subsequent":[239],"studies":[240,576,928,1081,1185,1290,1390],"found":[241,455,699,1045,1291],"also":[245,428,522,966,1400],"source":[248,836],"plasma":[250,253,363],"T3,":[251,402],"i.e.":[252,369],"largely":[255],"originates":[256],"as":[261,290,504,798,813,1011,1013,1105,1107],"T4,":[262,331],"peripheral":[271],"tissues":[272,361,591,941],"(5,":[273],"6).":[274],"To":[275,843],"understand":[276,299],"how":[277],"neurological":[286,628,638,671],"opposed":[291],"therapy,":[294],"critical":[297,774],"two":[300,1288],"properties":[301],"physiology.":[304],"First,":[305],"when":[306],"levels":[309,366,588,613,1294],"fall,":[310],"activity":[312,324,435,491,520,1273,1297],"increases":[313,325],"thanks":[314],"decreased":[316],"ubiquitination":[317,466],"enzyme":[320,1264,1278],"(7).":[321],"As":[322,996],"face":[328],"falling":[330],"net":[333],"effect":[334,1408],"homeostatic,":[336],"promoting":[337],"maintenance":[338],"levels.":[342],"Second,":[343],"expressed":[346,561,709,1262,1277],"endoplasmic":[349],"reticulum,":[350],"D2-generated":[352,666,716,743],"accumulate":[355],"nucleus":[358],"specific":[360],"while":[362,485],"remain":[367],"unchanged;":[368],"allows":[371],"local":[373],"control":[374,539],"signaling.":[378],"For":[379],"example,":[380,464],"sympathetic":[381],"stimulation":[382],"brown":[384,425],"adipose":[385,426],"tissue":[386,400,427,1285],"leads":[387],"cAMP":[389],"generation,":[390],"which":[391,508,581],"turn":[393],"induces":[394],"fills":[397],"up":[398],"crucial":[404],"adaptive":[407],"thermogenesis":[408],"(heat":[409],"generation":[410],"after":[411],"exposure":[412],"cold":[414],"high":[416,918],"caloric":[417],"diet)":[418],"(8).":[419],"example":[421],"illustrates":[429],"dynamic":[431],"changes":[432],"occur":[437],"settings":[439,457],"beyond":[440],"realm":[442],"homeostasis.":[446],"Indeed":[447],"\u201cproactive\u201d":[449],"roles":[450],"been":[454,621,739,866,950,1002],"ranging":[458],"development":[460,478,778],"metabolism;":[462],"accelerated":[468],"Hedgehog":[471],"signaling":[472,506],"pathway,":[473],"linking":[474],"deiodination":[475],"tibial":[481],"growth":[482,993],"plate":[483,994],"(9),":[484],"same":[488,601],"time":[489],"increased":[493],"G":[496],"protein-coupled":[497],"bile":[498,516],"acid":[499,1322],"receptor":[500],"1-mediated":[501],"(also":[502],"known":[503,812,1326],"TGR5)":[505],"cascade,":[507],"mediates":[509],"metabolic":[513,953],"effects":[514,634],"salts":[517],"(10).":[518],"induced":[523],"dietary":[526],"flavonols,":[527],"suggesting":[528],"potential":[530],"nutritional":[532],"pharmacological":[534],"manipulation":[535],"metabolism":[537],"(11).":[542],"homeostatic":[544],"proactive":[546],"functions":[547],"work":[553],"brain,":[556,999],"(12,":[562],"13).":[563],"Indirect":[564,754],"evidence":[565],"physiological":[568],"brain":[574,611,752,777,788,1166],"includes":[575],"thyroidectomized":[578],"rats":[579],"monoreplacement":[583],"fails":[584],"normalize":[586,1020],"but":[592,781,946,1054],"cerebral":[594],"cortex":[595],"spared":[597],"(14).":[598],"At":[599],"time,":[602],"knockout":[604],"mice":[605],"exhibit":[606],"substantial":[608],"reduction":[609],"but,":[614],"they":[619],"tested,":[622],"not":[624,1055,1131,1189,1217,1229,1255],"demonstrate":[625],"any":[626,1344],"overt":[627],"phenotype":[629,1370],"(15).":[630],"Thus,":[631,714],"whereas":[632,703,1314],"function":[639,672],"established,":[642],"regarding":[647],"mood":[651,1175],"exists":[652],"(16),":[653],"except":[654],"TSH":[657,1009,1021],"mechanism,":[659],"remains":[661,789],"proven":[664],"adult":[674],"humans.":[675],"observation":[677,764],"unexpected":[680],"spatial":[681],"dichotomy":[682],"currently":[683],"prevents":[684],"full":[686],"accounting":[688],"brain:":[696],"glial":[701,729,742,810],"cells,":[702],"receptors":[706],"predominantly":[708],"neurons":[711],"(17,":[712],"18).":[713],"its":[720,908],"proposed":[721,740],"effects,":[722],"must":[724,1371,1379],"somehow":[725],"transit":[726,783],"cytoplasm":[730],"nuclei":[733],"target":[735],"neurons;":[736],"has":[738,1192,1248],"acts":[745],"paracrine":[748],"fashion":[749],"(19).":[753],"support":[755],"hypothesis":[758],"taken":[761],"transporter":[768,770],"monocarboxylate":[769],"8":[771],"(20,":[779],"21),":[780],"iodothyronines":[785],"elucidated.":[792],"supply-side":[794],"situation":[795],"complex":[797,1147],"well;":[799],"mediobasal":[802],"expression":[805],"concentrated":[807],"specialized":[809],"cells":[811],"tanycytes,":[814],"located":[815,1318],"floor":[818],"infralateral":[820],"walls":[821],"third":[824],"ventricles.":[825],"This":[826,900],"location":[827],"suggests":[828],"cerebrospinal":[831],"fluid":[832],"may":[833],"hypothalamic":[840],"(22).":[842],"date,":[844],"there":[845],"no":[847],"identified":[848,1373],"genetic":[849,1389],"syndromes":[850],"involving":[851],"mutations":[852],"gene.":[856],"number":[859,926,1125],"single":[861,1452],"nucleotide":[862,1453],"polymorphisms":[863],"(SNPs)":[864],"identified,":[867],"best":[869],"being":[871],"Thr92Ala,":[872],"common":[874,903,974],"A-G":[875],"(T-C":[877],"complementary":[880],"forward":[881],"strand)":[882],"codon":[884,1214,1315],"92":[885,1215,1316],"predicts":[887],"Ala":[889],"Thr":[891],"substitution":[892,1208,1253,1355,1412],"(274":[893],"A-G,":[894],"D2-G/A;":[895],"GI":[896],"13654872;":[897],"rs225014)":[898],"(23).":[899,1244],"SNP":[901],"various":[905],"ethnic":[906],"groups:":[907],"allele":[909],"frequency":[910],"0.35":[912],"Caucasians":[914],"particularly":[917],"0.75":[920],"Pima":[922],"Indians.":[923],"A":[924,1146,1177],"growing":[925],"examined":[930],"correlations":[931],"between":[932,1004,1047,1093],"Thr92Ala":[934,962,1006,1056,1095,1135,1161,1184,1252,1270,1347,1354,1411],"disease":[937,978],"dysfunction":[939],"expressed,":[945],"results":[948,1119],"mixed":[951],"endpoints":[954,1138],"(23\u201327)":[955],"hypertension":[958],"(28\u201330).":[959],"Recently,":[960],"linked":[967],"susceptibility":[969],"generalized":[971],"osteoarthritis,":[972],"late-onset":[975],"articular":[976],"joint":[977],"(31);":[979],"interesting":[983],"result,":[984],"given":[985],"developing":[992],"(9).":[995],"associations":[1000,1046,1133],"reported":[1003],"level":[1010],"dose":[1015],"needed":[1018,1401],"(32,":[1022],"33).":[1023],"investigators":[1025],"failed":[1026,1341],"find":[1028,1132],"association":[1030,1092],"paroxetine":[1034],"depressed":[1037],"(34),":[1039],"study":[1042,1267],"China":[1044],"other":[1048,1183],"SNPs":[1050],"mental":[1052],"retardation":[1053],"(35).":[1057],"publication":[1059],"adds":[1065],"importantly":[1066],"because":[1070],"WATTS":[1072],"data":[1073],"set":[1074],"represents":[1075],"one":[1076,1378],"largest":[1079],"randomized":[1080],"(4).":[1086],"key":[1088,1178],"findings":[1089,1310,1386],"lower":[1098,1293],"baseline":[1099],"well-being":[1101],"alone,":[1104],"improvement":[1109],"combination":[1111],"compared":[1114],"monotherapy.":[1117],"These":[1118],"stand":[1120],"contrast":[1122],"smaller":[1127],"trials":[1128],"did":[1130],"cognitive":[1137,1173],"references":[1140],"(3)].":[1145],"clinical":[1148],"arises":[1150],"these":[1152,1309,1388],"findings:":[1153],"subset":[1156],"abnormal":[1162],"respect":[1164],"levels,":[1168],"thus":[1170],"susceptible":[1171],"defects?":[1176],"point":[1179],"underlying":[1180],"functional":[1193],"implications":[1194,1432],"protein.":[1197],"On":[1198],"score,":[1200],"jury":[1202],"still":[1204],"out.":[1205],"nonconservative":[1210],"(aliphatic":[1211],"polar),":[1213],"catalytic":[1220],"site":[1222],"enzyme,":[1225],"phylogenetically":[1230],"conserved:":[1231],"homologous":[1233],"position":[1234],"proline":[1236],"rodents":[1238],"glycine":[1240],"chicken":[1242],"vitro":[1246,1338],"analysis":[1247,1340],"shown":[1249],"does":[1254],"change":[1256],"kinetics":[1258],"transiently":[1261],"(32).":[1265],"One":[1266],"suggested":[1268],"decreases":[1271],"endogenously":[1276],"human":[1280,1303],"skeletal":[1283,1304],"muscle":[1284,1305],"(24).":[1286],"subsequent":[1289],"much":[1292],"(two":[1298],"orders":[1299],"magnitude)":[1301],"(36,":[1306],"37),":[1307],"calling":[1308],"into":[1311],"question.":[1312],"Furthermore,":[1313],"18-amino":[1321],"region":[1323],"regulation":[1331],"enzyme\u2019s":[1334],"ubiquitination,":[1335,1360],"mutational":[1339],"confirm":[1343],"impact":[1345],"protein":[1349],"stability":[1350],"(38).":[1351],"If":[1352],"relevant":[1357],"conditions":[1362],"factors":[1365],"bring":[1367],"out":[1368],"confirmed":[1375],"experimentally.":[1376],"Otherwise,":[1377],"consider":[1380],"possibility":[1382],"positive":[1385],"based":[1392],"linkage":[1394],"another":[1396],"locus.":[1397],"What":[1398],"prospective":[1404],"trial":[1405],"studying":[1406],"neuropsychiatric":[1415],"T3/T4vs.":[1419],"l-t4;":[1422],"will":[1424],"true":[1427],"test":[1428],"fascinating":[1431],"raised":[1433],"work.":[1437],"Disclosure":[1438],"Summary:":[1439],"authors":[1441],"nothing":[1443],"disclose.":[1445],"Type":[1446]},"counts_by_year":[{"year":2025,"cited_by_count":2},{"year":2024,"cited_by_count":1},{"year":2022,"cited_by_count":1},{"year":2019,"cited_by_count":2},{"year":2018,"cited_by_count":1},{"year":2017,"cited_by_count":1},{"year":2014,"cited_by_count":3},{"year":2013,"cited_by_count":1},{"year":2012,"cited_by_count":3}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}
