Relationships of serum free thyroxine and erythrocyte measures in euthyroid <i>HFE</i> C282Y homozygotes and control subjects: the HEIRS Study

Barton, James C.; Leiendecker–Foster, Catherine; Reboussin, D. M.; Adams, Paul C.; Rt, Acton; Eckfeldt, John H.

doi:10.1111/j.1751-553x.2009.01182.x

Cited by 5 publications

(3 citation statements)

References 20 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results indicated that the signals at HFE and TMPRSS6 were mediated through the MCV component of Hct and through Hb. This is in agreement with findings that patients with hereditary hemochromatosis have higher mean Hb and MCV, and lower mean RCC than controls [ 35 , 36 ], while in iron-deficiency states such as IRIDA, low values for Hb and MCV occur, with RCC being higher [ 2 , 37 ]. In both conditions, changes in Hb and MCV are in the opposite direction to RCC, consistent with our observations in the conditional analysis.…”

Section: Discussionsupporting

confidence: 91%

Replication and Characterization of Association between ABO SNPs and Red Blood Cell Traits by Meta-Analysis in Europeans

et al. 2016

View full text Add to dashboard Cite

Red blood cell (RBC) traits are routinely measured in clinical practice as important markers of health. Deviations from the physiological ranges are usually a sign of disease, although variation between healthy individuals also occurs, at least partly due to genetic factors. Recent large scale genetic studies identified loci associated with one or more of these traits; further characterization of known loci and identification of new loci is necessary to better understand their role in health and disease and to identify potential molecular mechanisms. We performed meta-analysis of Metabochip association results for six RBC traits—hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV) and red blood cell count (RCC)—in 11 093 Europeans from seven studies of the UCL-LSHTM-Edinburgh-Bristol (UCLEB) Consortium. We identified 394 non-overlapping SNPs in five loci at genome-wide significance: 6p22.1-6p21.33 (with HFE among others), 6q23.2 (with HBS1L among others), 6q23.3 (contains no genes), 9q34.3 (only ABO gene) and 22q13.1 (with TMPRSS6 among others), replicating previous findings of association with RBC traits at these loci and extending them by imputation to 1000 Genomes. We further characterized associations between ABO SNPs and three traits: hemoglobin, hematocrit and red blood cell count, replicating them in an independent cohort. Conditional analyses indicated the independent association of each of these traits with ABO SNPs and a role for blood group O in mediating the association. The 15 most significant RBC-associated ABO SNPs were also associated with five cardiometabolic traits, with discordance in the direction of effect between groups of traits, suggesting that ABO may act through more than one mechanism to influence cardiometabolic risk.

show abstract

Section: Discussionsupporting

confidence: 91%

Replication and Characterization of Association between ABO SNPs and Red Blood Cell Traits by Meta-Analysis in Europeans

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The association of free T4 with erythrocyte indices, including Hb, red blood cell count, MCV, RDW, and ferritin concentration, has been further assessed in euthyroid adults with or without C282Y homozygosity from the Haemochromatosis and Iron Overload Screening study. In this study, free T4 was positively correlated with Hb concentration and negatively correlated with RDW in those individuals without C282Y homozygosity [ 218 ].…”

Section: Thyroid Hormones and Anemiamentioning

confidence: 99%

The Role of the Multiple Hormonal Dysregulation in the Onset of “Anemia of Aging”: Focus on Testosterone, IGF-1, and Thyroid Hormones

Maggio

Vita

Fisichella

et al. 2015

International Journal of Endocrinology

View full text Add to dashboard Cite

Anemia is a multifactorial condition whose prevalence increases in both sexes after the fifth decade of life. It is a highly represented phenomenon in older adults and in one-third of cases is “unexplained.” Ageing process is also characterized by a “multiple hormonal dysregulation” with disruption in gonadal, adrenal, and somatotropic axes. Experimental studies suggest that anabolic hormones such as testosterone, IGF-1, and thyroid hormones are able to increase erythroid mass, erythropoietin synthesis, and iron bioavailability, underlining a potential role of multiple hormonal changes in the anemia of aging. Epidemiological data more consistently support an association between lower testosterone and anemia in adult-older individuals. Low IGF-1 has been especially associated with anemia in the pediatric population and in a wide range of disorders. There is also evidence of an association between thyroid hormones and abnormalities in hematological parameters under overt thyroid and euthyroid conditions, with limited data on subclinical statuses. Although RCTs have shown beneficial effects, stronger for testosterone and the GH-IGF-1 axis and less evident for thyroid hormones, in improving different hematological parameters, there is no clear evidence for the usefulness of hormonal treatment in improving anemia in older subjects. Thus, more clinical and research efforts are needed to investigate the hormonal contribution to anemia in the older individuals.

show abstract

“…28 In another referral and family based study, stage II-IV fibrosis or greater, was present in 18% male patients; 5.6% were cirrhotic. 29 The greatest influence on penetrance of genetic hemochromatosis is sex, with males more likely to have biochemical evidence of increased iron and clinical and histological disease of the liver as well as other organs due to iron overload. Data to suggest that this disparity in disease is mainly due to menstrual blood loss in women and subsequent lower iron stores comes from a study of women who had early menopause or hysterectomy before age 50 years.…”

Section: Penetrance Variabilitymentioning

confidence: 99%

Genetic Modifiers of Liver Injury in Hereditary Liver Disease

Ala¹,

Schilsky²

2011

Semin Liver Dis

View full text Add to dashboard Cite

The genetic background of patients with liver diseases modulates hepatic injury, with some individuals being predisposed to better defenses and regenerative capacity. In this review, we focus our description of this phenomenon on inherited disorders affecting the liver, with a particular emphasis on Wilson disease (WD), genetic hemochromatosis, and α-1 anti-trypsin disease (A1-AT). Wide variations in the clinical phenotype of WD may in part be related to the mutations of the ATP7B genotype, though modifier genes and environmental factors also likely play an important role. There is also a significant variability in the expression of iron overload in patients with genetic hemochromatosis that are homozygous for the C282Y mutation. Homozygosity for the A1-ATZ mutation is generally required for the development of liver disease in A1-AT although there is increasing evidence for modifier effects from a heterozygous genotype in other liver diseases.

show abstract

Relationships of serum free thyroxine and erythrocyte measures in euthyroid HFE C282Y homozygotes and control subjects: the HEIRS Study

Cited by 5 publications

References 20 publications

Replication and Characterization of Association between ABO SNPs and Red Blood Cell Traits by Meta-Analysis in Europeans

Replication and Characterization of Association between ABO SNPs and Red Blood Cell Traits by Meta-Analysis in Europeans

The Role of the Multiple Hormonal Dysregulation in the Onset of “Anemia of Aging”: Focus on Testosterone, IGF-1, and Thyroid Hormones

Genetic Modifiers of Liver Injury in Hereditary Liver Disease

Contact Info

Product

Resources

About