Graves’ Disease: Pathophysiology, Genetics and Management

Graves’ disease is an autoimmune disorder in which hyperthyroidism (over active thyroid) is caused by the autoantibodies against the TSH receptor. It is mainly characterized by the appearance of goiter. The symptoms are wide ranging as thyroid hormone affects many body systems. It is common in women and in people with age below than 40. Graves’ disease is caused by a combination of genetic and environmental factors while genetics being the main cause. Graves’ disease is not a single gene defect but has a complex pattern of inheritance. Today it is clear that genetic predisposition to Graves’ disease is caused by multiple genes. HLA gene is one the most studied gene predisposing to Graves’ disease. Lot of polymorphisms in this gene has been to be associated with the disease. Lymphoid tyrosine phosphatase encoded by the gene PTPN22 has been found to increase the risk of many autoimmune diseases including Graves’ disease. The best documented association of PTPN22 variants to autoimmune disorders including GD is rs2476601 (C1858T). Other genes associated with the risk of GD are thyrotropin receptor (TSHR), thyroglobulin gene, FCRL3, SCGB3A2, and CTLA4. This chapter will discuss in detail the genetics, pathophysiology, diagnosis and treatment of Graves’ hyperthyroidism.

АССОЦИАТИВНЫЕ СВЯЗИ ГЕНА ТИРЕОГЛОБУЛИНА С ПРОДУКТИВНЫМ ДОЛГОЛЕТИЕМ МОЛОЧНОГО СКОТА

Изучен полиморфизм гена тиреоглобулина в ассоциации с продолжительностью хозяйственного использования и продуктивностью коров. Генетический профиль популяции по совокупности частот встречаемости аллелей локуса тиреоглобулина выглядит следующим образом выявлено большинство коров-носителей аллеля С в гомозиготном состоянии до 7 лактации, однако увеличение животных с гетерозиготным генотипом наблюдалось в подвыборках 8 и 9 лактаций. В целом по изученной популяции распределение полиморфных генотипов было: TG5CС 63,5, TG5CT 32,1, TG5ТT 4,4 частота встречаемости по аллелям равна: С 0,80, Т 0,20. С увеличением возраста лактации продуктивность различается у коров с разными полиморфными генотипами. У первотелок наибольшая продуктивность установлена у особей с генотипом TG5ТT, от которых надоено на 77 кг больше, чем от гетерозиготных. Однако в дальнейшем высокая продуктивность была характерна для коров с генотипом TG5СС и TG5СT. Средний возраст в лактациях по всему изученному поголовью составляет 2,7. В динамике возраста удой в изученном стаде животных повышался до 7 лактации, максимальные значения которого по ней составили 72947300 кг. Для повышения рентабельности производства молока необходимо принимать меры по повышению продуктивного долголетия.Thyroglobulin gene polymorphism was studied in association with the duration of economic use and productivity of cows. The genetic profile of the population in terms of the frequency of occurrence of alleles of the thyroglobulin locus is as follows - the majority of cows carrying the C allele in a homozygous state up to 7 lactation were detected, however, an increase in animals with a heterozygous genotype was observed in subsamples of 8 and 9 lactations. In general, for the studied population, the distribution of polymorphic genotypes was: TG5CC - 63.5, TG5CT - 32.1, TG5TT - 4.4 the frequency of occurrence in alleles is: C - 0.80, T - 0.20. With increasing age of lactation, productivity differs in cows with different polymorphic genotypes. In heifers, the highest productivity was found in individuals with the TG5TT genotype, from which 77 kg more were fed than from heterozygous ones. However, in the future, high productivity was characteristic for cows with the genotypes TG5CC and TG5CT. The average age in lactations throughout the studied population is 2.7. In the dynamics of age, milk yield in the studied herd of animals increased to 7 lactation, the maximum values of which amounted to 7294-7300 kg. To increase the profitability of milk production, it is necessary to take measures to increase productive longevity.