engleski

Gene variants in young healthy subjects and their effects on biological variables of lipid status and obesity

The correlation of gene variants with biological variables or clinical assessments has not been well understood, especially among apparently healthy subjects. Human obesity is a multifactorial syndrome influenced by both environmental and genetic factors. Among gene variants found to be involved in body weight regulation and the development of obesity, particular attention has been paid to polymorphisms in the genes related to adipogenesis, energy expenditure, and insulin resistance. Peroxisome proliferator-activated receptors PPARs are members of the nuclear hormone receptor subfamily of ligand-dependent transcription factors. The isoform PPARG2 is mainly expressed in adipose tissue where it modulates the expression of target genes involved in adipocyte differentiation, insulin sensitivity and inflammatory processes. We explored the association of some genetic polymorphisms of: PPARG2, Pro12Ala ; adiponectin (ADIPOQ -11391G>A and 11377C>G) ; IL-6-174G>C ; TCF7L2 (rs7903146) ; eNOS -786T>C, estrogen receptor (ESR1alfa-TA): APOE ; ACE (I/D) ; MTHFR-677C>T ; LPL (PvuII+/-), with clinical variables: gender, age, BMI, and biological variables: triglycerides, cholesterol, HDL, LDL, CRP, homocysteine, glucose in 62 healthy young subjects (age range 20-35 y) of Croatian origin. Methods. The genotyping of PPARG2, IL-6, ACE, LPL, eNOS was performed by PCR-RFLP, TCF7L2, APOE, MTHFR, ADIPOQ, by real-time PCR and ESR1alpha by capillary electrophoresis. Linkage-disequilibrium likelihood-ratio tests between loci whose gametic phase is unknown (Slatkin & Excoffier, 1996) were performed, as implemented in Arlequin ver. 3.01 (Excoffier et. al., 2006). Associations of alleles, genotypes and haplotypes with biological variables were performed using UNPHASED-3.0.10. Sex, age, BMI was used as covariates. BMI was increased (>25) in 30% of subjects. Increased cholesterol values (>5.0 mmol/L) were found in 42.3% of subjects, LDL (>3.0 mmol/L) in 42.4%, triglycerides (>1.7 mmol/L) in 8.6%, glucose (>6.4 mmol/L) in 5.7%. Subjects with PPARG –Ala and IL-6-G variants had higher BMI (p=0.003) and higher cholesterol level (p=0.02) compared to subjects with PPARG2-Pro and IL-6-C. BMI was also increased in subjects with low level adiponectin gene variant (GG/GG). ESR1>19TA genotypes were significantly correlated to high LDL level (p=0.04). ADIPOQ-GG/GG genotypes/haplotypes were correlated to increased cholesterol and LDL values (p= 0.04, p=0.03 respectively). Combination of ADIPOQ-GG/GG and LPL+/+ resulted in increased cholesterol, LDL and trygliceride levels. Carriers of ADIPOQ-GG APOE-3/4, MTHFR-T/T had increased cholesterol, LDL, CRP and homocysteine levels. Subjects carrying both PPARG2 and IL-6 gene variants had a profile of obesity-related risk factors compared to subjects with one variant where AlaC/CC carriers had lower BMI and triglyceride levels. Adiponectin gene variants also represent predictive genetic risk marker for lipid status and obesity.

ESR1; LPL; APOE; obesity

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