GENETIC AND EPIDEMIOLOGICAL STUDIES ON THE ROLE OF ADIPONECTIN AND PTP1B IN THE METABOLIC SYNDROME, ACTA UNIVERSITATIS OULUENSIS D Medica 1054

The metabolic syndrome is a cluster of components predisposing to type 2 diabetes and\ncardiovascular disease. Abdominal obesity and insulin resistance seem to be central in the\nmetabolic syndrome, although no unifying pathophysiological mechanism is available. The aim\nof this thesis was to determine out how the variation in PTP1B and adiponectin gene as well as\nvariations in the plasma adiponectin concentration contribute to the risk of obesity related\ndiseases.\nPTP1B is a negative regulator of insulin signalling and therefore considered a candidate gene\nfor type 2 diabetes. In the first study, it was found that three PTP1B polymorphisms studied have\nnot strong impact on type 2 diabetes. However, one SNP may be slightly protective against type 2\ndiabetes, since it was more frequent in the healthy group compared to group of patients with type\n2 diabetes. Another SNP was associated with body mass index (BMI). The combination of certain\nalleles of PTP1B and LEPR (leptin receptor) genes was also associated to BMI.\nAdiponectin is an adipocytokine expressed in adipose tissue. It has insulin sensitizing effects\nin liver and muscle and it has also beneficial effects on cardiovascular health. In the second study,\nthe contribution of adiponectin genotypes with obesity-related phenotypes was studied. In\nCaucasians, the carriers of rare allele of Tyr111His polymorphism were more insulin resistant and\nat a higher risk of developing type 2 diabetes. In African-Americans, other polymorphisms were\nassociated with BMI and lipids. Thus, the effects of polymorphisms on obesity related phenotypes\nseemed to be different between ethnic groups.\nPlasma adiponectin levels were measured from different study groups. In the third study, it was\nfound out that low plasma adiponectin levels associated with different components of the\nmetabolic syndrome and there was a trend towards reductions in adiponectin with an increasing\nnumber of components. Fourth study indicated that baseline low adiponectin level associated with\na more than 2-fold risk for developing impaired glucose tolerance or type 2 diabetes in the followup\nstudy of normoglycemic middle-aged Finnish subjects. In the fifth study, plasma adiponectin\nlevels were measured from postmenopausal women receiving estrogen replacement therapy. We\nobserved a reduction in adiponectin levels in women having peroral estradiol which could be part\nof the "early harm" profile on cardiovascular risk factors of the peroral estrogen replacement\ntherapy detected in clinical trials.\nThese studies further strengthen the role of plasma adiponectin in the obesity related diseases\nand bring new information of polymorphisms in the adiponectin and PTP1B genes in different\npopulations.

ISBN-10:
978-951-42-6184-8
Kieli:
eng.
Sivumäärä:
141 s.
Tekijät:
Santaniemi Merja
Tuotekoodi 013973
20,00 €