Analysis of candidate genes in Polish families with obesity.
This study analyzes the relationship between risk factors related to overweight/obesity, insulin resistance, lipid tolerance, hypertension, endothelial function and genetic polymorphisms associated with: i) appetite regulation (leptin, melanocortin-3-receptor (MCR-3), dopamine receptor 2 (D2R)); ii) adipocyte differentiation and insulin sensitivity (peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), tumor necrosis factor-alpha (TNF-alpha)); iii) thermogenesis and free fatty acid (FFA) transport/catabolism (uncoupling protein-1 (UCP1), lipoprotein lipase (LPL), beta2- and beta3-adrenergic receptor (beta2AR, beta3AR), fatty acid transport protein-1 (FATP-1) and iv) lipoproteins (apoliprotein E (apoE), apo CIII). The 122 members of 40 obese Caucasian families from southern Poland participated in the study. The genotypes were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) or by direct sequencing. Phenotypes related to obesity (body mass index (BMI), fat/lean body mass composition, waist-to-hip ratio (WHR)), fasting lipids, glucose, leptin and insulin, as well as insulin during oral glucose tolerance test (OGTT) (4 points within 2 hours) and during oral lipid tolerance test (OLTT) (5 points within 8 hours) were assessed. The insulin sensitivity indexes: homeostasis model assessment of insulin resistance, whole body insulin sensitivity index, hepatic insulin sensitivity and early secretory response to an oral glucose load (HOMA-IR, ISI-COMP, ISI-HOMA and DELTA) were calculated. The single gene mutations such as C105 T OB and Pro115 Gln PPAR-gamma2 linked to morbid obesity were not detected in our group. A weak correlation between obesity and certain gene polymorphisms was observed. Being overweight (25 < BMI > or = 30 kg/m2) significantly correlated with worse FFA tolerance in male PPAR-gamma2 12Pro, LPL-H (G) allele carriers. Insulin resistance was found in female PPAR-gamma2 Pro12, TNF-alpha (-308A) and LPL-H (G) allele carriers. Hypertension linked to the PPAR-gamma2 Pro allele carriers was characterized by high leptin output during OLTT. We conclude that the polymorphisms we investigated were weakly correlated with obesity but significantly modified the risk factors of the metabolic syndrome.
Malczewska-Malec
Małgorzata
M
Department of Clinical Biochemistry, The Jagiellonian University Medical College, Kraków, Poland.
Wybranska
Iwona
I
Leszczynska-Golabek
Iwona
I
Partyka
Lukasz
L
Hartwich
Jadwiga
J
Jabrocka
Agata
A
Kiec-Wilk
Beata
B
Kwasniak
Małgorzata
M
Motyka
Marcin
M
Dembinska-Kiec
Aldona
A
D000328:Adult; D000367:Age Factors; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics; D004041:Dietary Fats / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005951:Glucose Tolerance Test; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D007473:Ion Channels; D020738:Leptin / Q000097:blood; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D024101:Mitochondrial Proteins; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics; D011044:Poland; D011110:Polymorphism, Genetic / Q000235:genetics*; D044104:Receptor, Melanocortin, Type 3 / Q000235:genetics; D011943:Receptors, Adrenergic, beta / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D000071256:Uncoupling Protein 1
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D002352:Carrier Proteins; D004041:Dietary Fats; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D044104:Receptor, Melanocortin, Type 3; D011943:Receptors, Adrenergic, beta; D017448:Receptors, Dopamine D2; D014409:Tumor Necrosis Factor-alpha; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; D008071:Lipoprotein Lipase