Bozina Tamara, Simić Iveta, Lovrić Jasna, Pećin Ivan, Jelaković Bojan, Sertić Jadranka, Reiner Zeljko
University of Zagreb, School of Medicine, Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Zagreb, Croatia.
Coll Antropol. 2013 Sep;37(3):801-8.
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.
过氧化物酶体增殖物激活受体γ(PPARG)和脂蛋白脂肪酶(LPL)在脂质稳态、胰岛素抵抗和脂肪生成中发挥重要作用,其基因变异性可被视为代谢综合征(MetSy)的预测性遗传标志物。本研究的目的是评估PPARG(Pro12Ala)和LPL PvuII(+/-)多态性与代谢综合征及其特征之间可能存在的关联。研究纳入了527名受试者。根据修改后的美国国家胆固醇教育计划成人治疗小组第三次报告的定义,将受试者分为代谢综合征组和对照组。使用聚合酶链反应-限制性片段长度多态性方法进行基因分型。在总样本中,LPL变异与腰围(χ2 = 7.263,自由度 = 2,p = 0.026)和体重指数(BMI)(χ2 = 6.549,自由度 = 2,p = 0.038)相关,其中PvuII(+/+)基因型携带者腰围增加(特定PvuII(+/+)与其他基因型分析χ2 = 7.033,p = 0.008)和BMI增加(特定PvuII(+/+)与其他基因型分析χ2 = 5.154,p = 0.023)的风险最高。LPL基因变异也与高密度脂蛋白胆固醇(HDL-C)水平相关(χ2 = 6.901,自由度 = 2,p = 0.032),与其他基因型相比,PvuII(-/-)基因型携带者的HDL-C值更高(特定Pvu(+/+)与其他基因型分析χ2 = 6.504,p = 0.011)。此外,PvuII(-)等位基因携带者的血糖显著更低(基于等位基因的分析增加值 = -0.0878,χ2 = 5.878,自由度 = 1,p = 0.015)。在男性人群中,检测到PPARG和LPL之间存在显著相互作用,影响HDL-C水平(χ2 = 11.790,自由度 = 1,p = 0.0006),表现为Ala/PvuII(+)导致HDL-C值最低(特定Ala/Pvu(+)与其他基因型分析χ2 = 11.750,p = 0.0006)。根据所得结果,LPL和PPARG基因变异可能是肥胖和脂质状态的易感因素,有助于代谢综合征的发生发展,尤其是在男性中。由于HDL-C具有抗动脉粥样硬化功能,鉴定与HDL-C相关的基因变异可为基因型-表型关系提供有用信息。由于PPARG和LPL基因与性别的相互作用似乎很显著,这可能为预防代谢和心血管疾病提供个性化的行为建议。