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Genetic predisposition to elevated serum thyrotropin is associated with exceptional longevity.

ABSTRACT: Exceptional longevity is associated with raised serum TSH.The aim of this study was to examine whether offspring of people with exceptional longevity have elevated serum TSH and whether specific single nucleotide polymorphisms (SNPs) in the TSH-B gene and TSH receptor (TSHR) gene are associated with this phenotype.We measured serum TSH and free T(4) in Ashkenazi Jewish centenarians (n = 232; median age, 97 yr), their offspring (n = 366; median age, 69 yr), and age-matched controls without familial longevity (n = 163; median age, 70 yr). We determined TSH heritability, its distribution, and association with SNPs in the TSH-B and TSHR genes.Offspring had higher median serum TSH [1.68 mIU/liter (97.5% confidence interval, 0.65 to 4.79 mIU/liter)], compared to controls [1.50 mIU/liter (97.5% confidence interval, 0.63 to 3.93 mIU/liter); P = 0.02], with estimated heritability of 0.33 (P = 0.004). Allele frequency of two SNPs in the promoter/enhancer region of TSHR gene, associated with increased serum TSH, was higher in centenarians and their offspring compared to controls (rs10149689 G allele frequency, 0.57 and 0.53 vs. 0.48; P = 0.001 and P = 0.08; odds ratio, 1.56 and 1.22, respectively; and rs12050077 A allele frequency, 0.57 and 0.53 vs. 0.46; P = 0.0001 and P = 0.01; odds ratio, 1.68 and 1.32, respectively). Linkage disequilibrium between the two SNPs was high (r(2) = 0.95), suggesting interaction between them. Furthermore, GA haplotype frequency was significantly higher among centenarians and offspring compared to controls (0.57 and 0.53 vs. 0.46; P = 0.0001 and P = 0.01, respectively).A heritable phenotype characterized by raised serum TSH is associated with human longevity. Carriers of rs12050077 and rs10149689 SNPs in the TSHR have higher serum TSH, possibly contributing to decreased thyroid function and longevity.

SUBMITTER: Atzmon G

PROVIDER: S-EPMC2795660 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Genetic predisposition to elevated serum thyrotropin is associated with exceptional longevity.

Atzmon Gil G Barzilai Nir N Surks Martin I MI Gabriely Ilan I

The Journal of clinical endocrinology and metabolism 20091016 12

<h4>Context</h4>Exceptional longevity is associated with raised serum TSH.<h4>Objective</h4>The aim of this study was to examine whether offspring of people with exceptional longevity have elevated serum TSH and whether specific single nucleotide polymorphisms (SNPs) in the TSH-B gene and TSH receptor (TSHR) gene are associated with this phenotype.<h4>Design/setting/patients</h4>We measured serum TSH and free T(4) in Ashkenazi Jewish centenarians (n = 232; median age, 97 yr), their offspring (n ...[more]

PMID: 19837933

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Project description:IntroductionThyroid dysfunction is a highly prevalent yet under-recognized complication in hemodialysis patients. In the general population, hypothyroidism has been associated with endothelial dysfunction due to impaired vasodilator synthesis and activity. Little is known about the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with endothelial function in hemodialysis patients.MethodsIn a secondary analysis of 99 patients from the Anti-inflammatory and anti-oxidative nutrition in hypoalbuminemic dialysis patients (AIONID) trial, we examined measurements of serum TSH and endothelial function ascertained by fingertip digital thermal monitoring (DTM), a novel method used to measure micro-vascular reactivity, collected within a 90-day period. DTM was used to measure changes in fingertip temperature during and after an ischemic stimulus (blood pressure cuff occlusion) as an indicator of changes in blood flow, and two DTM indices were assessed, namely adjusted (a) Temperature Rebound (TR), defined as the maximum temperature rebound post-cuff deflation, and adjusted (b) Area Under the Temperature Curve (TMP-AUC), defined as area under the curve between the maximum and minimum temperatures. We examined the relationship between serum TSH with impaired TR (separately) and TMP-AUC (both defined as less than the median level of observed values) using multivariable logistic regression.FindingsIn unadjusted and case-mix analyses, higher serum TSH levels (defined as the three highest quartiles) were associated with lower (worse) TR (ref: lowest TSH quartile): ORs (95% CI) 2.64 (1.01-6.88) and 2.85 (1.08-7.57), respectively. In unadjusted and case-mix analyses, higher TSH levels were associated with lower (worse) TMP-AUC: ORs (95% CI) 2.64 (1.01-6.88) and 2.79 (1.06-7.38), respectively.DiscussionIn HD patients, higher serum TSH levels were associated with worse micro-vascular reactivity measured by DTM. Further studies are needed to determine if thyroid hormone supplementation improves endothelial function in hemodialysis patients with lower levels of thyroid function.

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Genetic predisposition to elevated serum thyrotropin is associated with exceptional longevity.

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Genetic predisposition to elevated serum thyrotropin is associated with exceptional longevity.

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