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.