Genetic analysis technique finds missing link between thyroid function and lipid profile

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Thyroid hormones are amino acid-based molecules produced by the thyroid gland. Involved in the direct or indirect regulation of key metabolic pathways, these molecules play an essential role in the development and normal functioning of the body. The mechanism by which thyroid hormones exert their effect on each other and other metabolic pathways is complex, but a two-way feedback loop is central to their biological activity. The disruption of the feedback loop that controls their production affects other biochemical pathways, causing various conditions, including those related to the cardiovascular system, liver function or bone development.

Several clinical studies have shown the effect of thyroid hormones on lipid levels: whether treating patients with thyroid hormone analogues improves their lipid levels, for example, or that thyroid hormones are associated with the metabolism of glycolipids and an increased risk of cardiovascular disease (CVD). These results highlight the possibilities of predicting the risk of lipid-related diseases or of designing a treatment strategy for CVD based on thyroid hormones. But such efforts would require the basis of a biological cause-and-effect relationship between thyroid hormones and lipid profile, an association that has yet to be proven.

It should be noted that the results of previous clinical studies, as intriguing as they are, have been unable to attribute thyroid hormones as the probable cause of the change in the lipid profile. Indeed, many confounding factors could have impacted both, blurring the cause-and-effect relationship between thyroid function and lipid profiles. Additionally, the observed relationship between the two may reflect reverse causality, where the change in lipid profile affected thyroid function. Thus, to take advantage of the observed association between thyroid function and serum lipid profile to design treatment strategies for lipid-related diseases, a better understanding of their causal dynamics becomes imperative.

Now, a team of researchers led by Dr Yi-Da Tang, Department of Cardiology, Peking University, in their article recently published in Chinese Medical Journal, presented a scientific basis for identifying thyroid function as a causative factor capable of affecting serum lipid levels. The team genetically analyzed the epidemiological data using a method called Mendelian Randomization (MR). RM is based on the assumption that genetic alleles are randomly matched in the population and act as proxies for environmental exposures that alter the risk of biological disease in a way that is less likely to be affected by factors behavioral, social or physiological confusion. Dr Tang, who is also the corresponding author of the study, explains, “As we tried to decipher the association between thyroid function and lipid profile, MRI came up with a solution to mimic a perfectly randomized controlled trial. designed. The approach allowed us to protect beyond confounding factors and the risk of reverse causation, and observe if there is a hidden causal effect of thyroid function on lipid-related diseases. ”

In their study, the researchers analyzed the genotype data of thousands of people from two datasets of genome-wide association studies (GWAS). For clinical measurements of thyroid function, they considered the levels of thyrotropin (TSH), free thyroxine (FT4), the ratio of free triiodothyronine (FT3) and FT4 (FT3: FT4) and anti-thyroid peroxidase antibodies ( TPOAb), as known essential thyroid traits. be linked to various illnesses. Then, from the GWAS, they identified 115 single nucleotide polymorphisms that represented genetic variants of thyroid function traits. Using magnetic resonance analysis, the researchers assessed the effect of each of the selected genetic variants for thyroid function on selected traits of lipid metabolism at the population level. They found that as potential causal factors for altered lipid levels, genetically altered levels of two of the selected thyroid traits, TSH level and FT3: FT4 ratio, were linked to elevated TC and FT4 levels. LDL of individuals. However, the genetically predicted FT4 level and TPOAb concentration were not associated with any of the serum lipid traits.

The team’s findings establish a distinct association between thyroid function and serum lipid metabolism. Interpreting the clinical significance of their result, Professor Tang concludes: “Our study highlights the importance of the pituitary-thyroid-cardiac axis in diseases linked to dyslipidemia. As we have proven the causal association, patients with thyroid disease or those on replacement therapy should pay attention to the thyroid trait and serum lipid profiles to prevent the development of cardiometabolic disease. ”

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Reference

Original article title: Assessment of the causal association between thyroid function and lipid metabolism: A Mendelian randomization study

Newspaper: Chinese Medical Journal

DOI: https: //do I.org /ten.1097 /cm9.0000000000001505

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