Effects of lipoprotein lipase and peroxisome proliferator-activated receptor-gamma gene variants on metabolic syndrome traits

Scientific paper - Original scientific paper

• Title (croatian): Utjecaj polimorfizama gena za lipoprotein lipazu i receptora za aktivator proliferacije peroksisoma-gama na sastavnice metaboličkog sindroma
• Author: Tamara Božina
• Author: Iveta Šimić
• Author: Jasna Lovrić
• Author: Ivan Pećin
• Author: Bojan Jelaković
• Author: Jadranka Sertić
• Author: Željko Reiner
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences

Abstract (english)

Peroxisome proliferator activated receptor-gamma (PPARG) and lipoprotein lipase (LPL) play important role in lipid homeostasis, insulin resistance and adipogenesis, and their gene variability could be considered as predictive genetic markers for metabolic syndrome (MetSy). The aim of the study was to estimate possible associations of PPARG (Pro12Ala) and LPL PvuII (+/-) polymorphisms with MetSy and its traits. Study included 527 subjects. According to the modified National Cholesterol Education Program Adult Treatment Panel III definitions, subjects were classified into the metabolic syndrome group and control group. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism methods. In the total sample, LPL variants were associated with waist circumference (chi2 = 7.263, d.f = 2, p = 0.026) and with BMI (chi2 = 6.549, d.f = 2, p = 0.038), where PvuII (+/+) genotype carriers had the highest risk for increased waist circumference (specific PvuII (+/+) vs. others analysis chi2 = 7.033, p = 0.008) and increased BMI (specific PvuII( +/+) vs. others analysis chi2 = 5.154, p = 0.023). LPL gene variants were also associated with HDL-C levels (chi2 = 6.901, d.f = 2, p = 0.032), where PvuII (-/-) genotype carriers had higher HDL-C values in comparison to others (specific Pvu (+/+) vs. others analysis chi2 = 6.504, p = 0.011). Furthermore, PvuII (-) allele carriers had significantly lower glucose (allele based analysis Add Value = -0.0878, chi2 = 5.878, d.f. = 1, p = 0.015). Significant interaction was detected between PPARG and LPL that affected HDL-C levels in male population (chi2 = 11.790, d.f = 1, p = 0.0006) in the manner that Ala/PvuII(+) contributed to the lowest HDL-C values (Specific Ala/ Pvu(+) vs. others analysis was chi2 = 11.750, p = 0.0006). According to obtained results LPL and PPARG gene variants could be susceptibility factors of obesity and lipid status, contributing to development of MetSy, particularly in males. Because of antiatherogenic function of HDL-C, the identification of genetic variants associated with HDL-C can provide useful information related to genotype-phenotype relationships. Since the interplay between PPARG and LPL gene and gender seems to be significant it could point to the personalized behavioural recommendations for prevention of metabolic and cardiovascular diseases.

Abstract (croatian)

Receptor za aktivator proliferacije peroksisoma tip g (PPARG) i lipoprotein lipaza (LPL) imaju važnu ulogu u lipidnoj
homeostazi, inzulinskoj rezistenciji i adipogenezi i stoga se njihova genska varijabilnost može smatrati mogućim
prediktivnim biljegom metaboličkog sindroma (MetSy). Cilj istraživanja bio je ispitati povezanosti između polimorfizma
PPARG (Pro12Ala) i LPL PvuII (–/+) s MetSy i njegovim sastavnicama. U studiju je bilo uključeno 527 ispitanika.
Prema kriterijima američkog programa za edukaciju o kolesterolu (National Cholesterol Education Program –
Third Adult Treatment Panel, NCEP-ATP III) ispitanici su podijeljeni u skupinu s metaboličkim sindromom i kontrolnu
skupinu. Genotipizacija je provedena metodama temeljenim na polimeraznoj lančanoj reakciji i analizi duljine
restrikcijskih ulomaka (PCR-RFLP). U ukupnom uzorku LPL varijante su bile povezane s opsegom struka (c2=7.263,
d.f.=2, p=0.026) i s BMI (c2=6.549, d.f.=2, p=0.038), pri čemu su nosioci genotipa LPL PvuII (+/+) imali najveći rizik
za povećani struk (specifični PvuII (+/+) vs. ostali c2=7.033, p=0.008) i povećani BMI (specifični Pvu II(+/+) vs. ostali
c2=5.154, p=0.023). LPL genske varijante su također povezane s razinom HDL-C (c2=6.901, d.f.=2, p=0.032), pri
čemu su nosioci genotipa PvuII (–/–) imali više vrijednosti HDL-C u odnosu na ostale (specifični Pvu (+/+) vs. ostali
c2=6.504, p=0.011). Nosioci alela PvuII (–) su također imali značajno niže vrijednosti glukoze (Add Value=–0.0878,
c2=5.878, d.f.=1, p=0.015). Uočena je značajna interakcija između PPARG i LPL s utjecajem na razine HDL-C u muškoj populaciji (c2=11.790, d.f.=1, p=0.0006), pri čemu su nosioci Ala/PvuII(+) imali najniže vrijednosti HDL-C
(specifični Ala/Pvu(+) vs. ostali c2=11.750, p=0.0006). Na osnovi dobivenih rezultata varijante gena LPL i PPARG bi se
mogle ubrojiti u genetičke čimbenike povećane podložnosti za razvoj debljine i lipidnog statusa koji doprinose razvoju
MetSy, posebno u muškoj populaciji. Zbog antiaterogene uloge koju ima HDL-C, identifikacija genetičkih varijacija
povezanih s HDL-C može rezultirati korisnim podacima u svrhu procjene genetičkog rizika. U tom smislu dobiveni
podaci podupiru važnost ispitivanja interakcija gena LPL i PPARG sa svrhom stvaranja personaliziranih preporuka
ponašanja i s konačnim ciljem prevencije metaboličkih i kardiovaskularnih bolesti.

• Keywords (english): Adult; Female; Genetic Variation; Genotype; Humans; Lipoprotein Lipase/genetics; Lipoprotein Lipase/metabolism; Male; Metabolic Syndrome X/genetics; Metabolic Syndrome X/metabolism; Middle Aged; PPAR gamma/genetics; PPAR gamma/metabolism; Polymorphism, Genetic
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Collegium Antropologicum
• Numbering: vol. 37, no. 3, pp. 801-808
• p-ISSN: 0350-6134
• URN:NBN: urn:nbn:hr:105:596949
• Publication: 2013-09
• Document URL: https://hrcak.srce.hr/118222
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-27 20:11:26