Endocrinology is a rapidly developing discipline in recent years, and the study of genes is also an emerging and popular direction. With the deepening of research, more and more studies have been focused on the connection between genes and endocrine diseases, so this paper is a review of this. I. Genes and diabetes mellitus and its chronic complications 1. Genes and diabetes mellitus There are many studies on the association between genes and diabetes mellitus, but the conclusions are different. Regarding the study of mitochondrial gene mutations and diabetes, more than 30 families and 100 cases of mutation carriers have been reported so far in China. More than 20 mutation sites are known, but the mtDNA transfer ribonucleic acid leucine tRNALeu (UUR) gene 3243A →G point mutation is still the most common mutation site. Studies suggest that mitochondrial gene mutations cause diabetes by mechanisms such as impaired oxidative phosphorylation, programmed β-cell death, disruption of calcium ion homeostasis and down-regulation of nucleoprotein genes. In recent years, some progress has been made on the relationship between vitamin D receptor genes and type 1 diabetes, and McDermott et al. found that the Bsm I locus polymorphism of the vitamin D receptor gene was significantly associated with insulin secretion in three family lines with type 1 diabetes. The relationship between vitamin D receptor gene and type 2 diabetes is less studied. The study by Fengying Liu et al. suggested that the variation of vitamin D receptor may alter insulin response by affecting the differentiation of B cells, thus causing impaired insulin secretion, which is associated with the occurrence of type 2 diabetes. 2. genes and chronic complications of diabetes Regarding genes and chronic complications of diabetes, there are more studies on diabetic nephropathy. susztak et al [6] applied gene microarrays to compare the renal gene expression in db-db mice and streptozotocin (STZ) induced diabetic mice. Only 40 transcripts were specifically expressed in the kidney of db-db mice and STZ-induced diabetic mice compared to normal mice, and there was only a 12-13% overlap between these two groups. Makino et al. compared the expression profiles of glomerular genes in db-db mice, db-m mice during the hyperglycemic proteinuria-free phase and DN microproteinuria phase using cDNA gene microarrays and found that The expression of hypoxia-inducible factor 21, nephrin B2, glomerular epithelial protein 21 and Pod21 were upregulated in db-db mice during the microproteinuria phase. The expression of genes related to pedunculocyte structure such as coactivator 4α and dystrophin glycan (DG1) was also increased. Abnormal expression of these genes may be associated with the development of early diabetic glomerulopathy in patients with type 2 diabetes.The results of Wong et al. showed that TGF-β1 gene T29 →C polymorphism was associated with the development of diabetic nephropathy (DN). CGRP binds to kidney-specific receptors and exerts a strong diastolic effect, especially in the small inlet artery, which reduces resistance more significantly than the small outlet artery, thus increasing renal blood flow and leading to “high perfusion, high pressure, and high filtration” in the glomerulus. “GluT1 gene polymorphisms may be associated with the prognosis of DN patients, but Zintzaras et al [11], through a meta-analysis of the relevant literature, concluded that the relationship between GluT1 gene polymorphisms and susceptibility to DN is unclear, and no correlation was found in larger clinical trials; and the correlation between the two was found in smaller clinical trials. The correlations were found in smaller clinical trials with a smaller number of cases. The BRAF gene is a downstream signaling molecule of RET and RAS. It encodes a B-type mitogen-activated protein kinase-dependent kinase (RAF) that is a key component of the RAS (a G protein)/RAF (mitogen-activated protein)/MEK (extracellular signal-regulated kinase)/MARK (mitogen-activated protein kinase) signaling pathway. A key component of the RAS/RAF/MEK (mitogen-activated protein kinase)/MARK (mitogen-activated protein kinase) signaling pathway, which regulates cell growth, proliferation and apoptosis and may lead to tumor formation when altered. The relationship between BRAF mutations and thyroid cancer has become a hot topic of current research. The first BRAF gene mutation was detected in undifferentiated/lowly differentiated carcinoma by Nikiforova et al. (11.1%), and subsequently many researchers have come to a more consistent conclusion. The PTEN gene, also known as MMAC1 or TEP1, is an oncogene discovered in the last decade and plays an important role in tumorigenesis, development and metastasis by regulating many important biological behaviors such as cell growth, proliferation, differentiation, apoptosis, adhesion and migration. It has been shown that it can dephosphorylate phosphatidylinositol such as PIP3, a major signaling molecule in the PI-3 K signaling pathway, thus playing an important negative regulatory role on tumors[. The study by Maozhu Li et al. [showed that PTEN has an important role in the evaluation of thyroid cancer progression, metastasis and prognosis, and its expression level is expected to be a reference indicator to determine the course and prognosis of thyroid cancer. Rapheal et al. found that cytokeratin 219 (CK219) was a useful marker for differentiating papillary thyroid carcinoma from benign hyperplastic follicles, follicular adenoma, and follicular carcinoma in a study of frozen sections of the thyroid gland. CK219 mRNA was found to be expressed in 100% of the thyroid cancer group and was significantly higher than that in the normal thyroid group, adenoma group, nodular goiter group and Hashimoto’s disease group, with statistically significant differences. Genes and autoimmune thyroid disease Graves’ disease, Hashimoto’s thyroiditis and idiopathic hypothyroidism are collectively known as autoimmune thyroid disease (AITD). T-cell activation requires recognition of a dual signaling system, namely the first signal provided by the MHC2 antigenic peptide and the costimulatory signal provided by the costimulatory molecule. The balance between positive and negative co-stimulatory molecules is important for the initiation, onset and development of autoimmunity. In addition to CTLA24 (cytotoxic T lymphocyte antigen24, CTLA24), PD21 (programmed death21, PD21) is a newly discovered negative costimulatory molecule that plays a role in the development of many autoimmune diseases. PD21 is a newly discovered negative co-stimulatory molecule, and PD21Ig or anti-PD21 monoclonal antibody plays an important role in the immunotherapy of autoimmune diseases, organ transplantation and tumors. Studies in PD21-deficient mice of different genetic backgrounds have demonstrated that PD21 plays a negative immunomodulatory role in vivo and plays an important role in the maintenance of peripheral immune tolerance. PD21 knockout NOD mice are more susceptible to type 1 diabetes than normal NOD mice. Genes and congenital primary hypothyroidism Congenital primary hypothyroidism is one of the most common endocrine disorders in children, with a prevalence of 1 in 3,000 to 1 in 4,000, and if not treated promptly and appropriately, children can suffer from severe mental retardation and growth disturbances. Although the vast majority of cases are epidemic, familial cases can still be seen clinically, and recent foreign studies have proposed some related genes, suggesting a possible genetic cause of the disease. The genes identified so far can be divided into two categories, one related to the embryonic development of the thyroid gland, such as TSH R, G sα, TTF-Ⅰ, TTF-Ⅱ and Pax8 genes, and patients carrying mutations in these genes have varying degrees of abnormal thyroid development. CT8 gene, patients with these mutations usually have goiter. Since 80%-85% of patients with congenital primary hypothyroidism have abnormal embryonic development of the thyroid gland, it is an important entry point to investigate the genes that regulate the embryonic development of the thyroid gland. Comprehensive domestic and foreign research results have shown that, at present has found the low thyroid related genes can not be used to explain the pathogenesis of most congenital primary hypothyroidism, to completely elucidate the pathogenesis of congenital primary hypothyroidism, need to further explore and explore new genes, study its regulatory factors and environmental factors. Third, genes and obesity genetic hypothesis that obesity, in the human genome can promote positive energy balance and lead to obesity gene frequency is quite high. There are many explanations, most scholars use “thrifty gene doctrine” to explain this phenomenon. The “thrifty gene theory” suggests that humans evolved in an environment of food scarcity and laborious work, and gradually developed a set of mechanisms to cope with food scarcity, that is, the opening of the thrifty gene. This facilitated adaptation to the harsh environment of the time, but when things are abundant today its continued role leads to obesity and a host of diseases that adversely affect humans. Because of the significant role of genes in obesity, the search for susceptibility genes for obesity has been dedicated since the 1990s. In recent years, individual single gene mutations may be associated with obesity in small sample studies, and leptin receptor genes have been shown to have a significant effect on weight change. Opioid and melanogen genes, hormone pro-converting enzyme genes and melanocortin receptor genes are the hot spots of research in recent years. However, because of the many causes of obesity, it is not yet possible to determine which gene determines obesity. Fourth, the gene and hyperlipidemia 2002 China’s population nutrition and health status survey results show that China’s adult dyslipidemia prevalence rate of 18.6%, estimated that the national dyslipidemia existing sufferers 160 million. Among them, 2.9% are hypercholesterolemia, 11.9% are hypertriglyceridemia, 7.4% are low HDL, and 3.9% have borderline elevated blood cholesterol. The overweight rate of adults in China is 22.8%, and the obesity rate is 7.1%. Hyperlipidemia is not only a serious health hazard, but also a major risk factor for cardiovascular diseases such as coronary heart disease and atherosclerosis. Numerous epidemiological surveys have shown that lipid and apolipoprotein levels increase with age and are influenced by multiple genes and factors. Lipoprotein lipase (LPL) is a key enzyme in human lipid metabolism and is expressed in most tissues in the body, especially in skeletal muscle, cardiac muscle and arterial tissue, and is also secreted by macrophages. Its activity is an important factor affecting lipid levels. Studies at home and abroad have found that multiple genetic loci variants in the non-coding region of the LPL gene can lead to a decrease in LPL activity and affect lipid levels in vivo. Epidemiological studies suggest a significant association between human apolipoproteinΕ (ApoΕ) gene polymorphisms and lipid levels, and a significant effect on lipid concentrations. The association of ApoΕ polymorphisms with coronary artery disease (coronary heart disease) and its severity has also been shown. Molecular genetic studies have shown that non-functional pituitary adenomas are monoclonal in origin and that a small proportion of these tumors exhibit autosomal dominant symptoms, namely multiple endocrine neoplasia type I (MEN1), which is associated with mutations in the tumor suppressor gene MEN1; other tumors are associated with loss of heterozygosity on chromosome 11q13. 30% of growth hormone adenomas have dominant mutations in the Gas gene, but this mutation has a significant effect on blood lipid concentrations. The mutation of the Gas gene is dominant in 30% of growth hormone adenomas, but it is less frequent in other pituitary adenomas. It has been shown that in non-functional pituitary adenomas, there can be a decrease in retinoid X receptors, estrogen receptors and thyroid hormone receptors, which may be related to hormonal regulation. However, the relationship between these factors and pituitary adenomas remains unclear. Epidermal growth factor receptors are overexpressed in 80% of nonfunctional pituitary adenomas but not in functional pituitary adenomas; in vitro, epidermal growth factor promotes the growth of nonfunctional pituitary adenomas, whereas nonfunctional pituitary adenomas upregulate epidermal growth factor mRN. Familial pituitary cell hyperplasia and tumorigenesis are preceded by alterations in at least 3 specific genes. Hypothalamic hormones, estrogen and growth factors may enhance genetic instability by altering the pituitary internal environment in a way that favors tumorigenesis, with mutations in the genes and eventual monoclonal expansion. However, since most endocrine diseases are not caused by a single gene mutation and involve many genes, gene therapy cannot be applied to clinical practice effectively. The research on the genetic mechanism of endocrine diseases has a bright future and a long way to go.