title: Obesity-related derangements of coagulation and fibrinolysis: a study of obesity-discordant monozygotic twin pairs.
abstract: Coagulation and fibrinolytic activities are under strong genetic control. We studied the effects of acquired obesity, independent of genetic factors on coagulation and fibrinolysis activities in obesity-discordant healthy monozygotic (MZ) twin pairs. Fourteen obesity-discordant (BMI within-pair difference >3 kg/m(2)) and 10 concordant (BMI difference <2 kg/m(2)) MZ twin pairs were identified from the nationwide FinnTwin16 study. Body composition (dual-energy x-ray absorptiometry), abdominal fat distribution (magnetic resonance imaging), liver fat (magnetic resonance spectroscopy), high sensitivity C-reactive protein, insulin sensitivity (euglycemic hyperinsulinemic clamp), and a panel of different markers of blood coagulation and fibrinolysis in the fasting state were measured. Strong resemblance was observed in most coagulation factors within all twin pairs, with the intraclass correlations ranging from 0.73 to 0.97, P < 0.03. However, the activities of fibrinogen and FIX, FXI, and FXII, and plasminogen activator inhibitor-1 (PAI-1) activities were increased in the obese co-twins (P < 0.05) and strongly correlated with the measures of adiposity, inflammation, and insulin resistance (r = 0.32-0.73, P < 0.05) among the twin individuals. Intrapair differences in fibrinogen and PAI-1 correlated with those in BMI, adiposity, and fasting insulin levels (r = 0.40-0.58, P < 0.05) indicating the independent effect of obesity. Derangements of blood coagulation and fibrinolysis are present already in early adulthood in obese subjects. Acquired obesity, independent of genetic factors, increases the activities of fibrinogen and activities of FIX, FXI, FXII, and PAI-1. This study confirms the mechanisms of simultaneous activities of intrinsic coagulation factors and impaired fibrinolysis predisposing obese subjects to thrombosis.
authors.affiliation: Obesity Research Unit, Department of Medicine, Division of Internal Medicine and Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland. sanna.kaye@hus.fi
authors.forename: Sanna M
authors.initials: SM
authors.lastname: Kaye
authors.forename: Kirsi H
authors.initials: KH
authors.lastname: Pietiläinen
authors.forename: Anna
authors.initials: A
authors.lastname: Kotronen
authors.forename: Lotta
authors.initials: L
authors.lastname: Joutsi-Korhonen
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Järvinen
authors.forename: Angela
authors.initials: A
authors.lastname: Silveira
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.forename: Riitta
authors.initials: R
authors.lastname: Lassila
authors.forename: Aila
authors.initials: A
authors.lastname: Rissanen
mesh_terms: D050153:Abdominal Fat / Q000378:metabolism*; D015502:Absorptiometry, Photon; D000328:Adult; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001823:Body Composition; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D005164:Factor IX / Q000378:metabolism; D005172:Factor XI / Q000378:metabolism; D005174:Factor XII / Q000378:metabolism; D005215:Fasting; D005234:Fatty Liver / Q000150:complications / Q000378:metabolism*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance; D008279:Magnetic Resonance Imaging; D008297:Male; D009765:Obesity / Q000097:blood / Q000150:complications / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D014430:Twins, Monozygotic
chemical_list: D001779:Blood Coagulation Factors; D017395:Plasminogen Activator Inhibitor 1; D005164:Factor IX; D005174:Factor XII; D005340:Fibrinogen; D002097:C-Reactive Protein; D005172:Factor XI