Dietary glycemic index and glycemic load mediate the effect of CARTPT rs2239670 gene polymorphism on metabolic syndrome and metabolic risk factors among adults with obesity

Abstract

Introduction: The importance of genetic and dietary factors in occurrence and progression of chronic diseases such as metabolic syndrome (MetS) has been established. However, complex interrelationships, including direct and indirect effects of these variables are yet to be clarified. So, our aim was to investigate the mediating role of glycemic indices in the relationship between CARTPT rs2239670 polymorphism, socio-demographic and psychological factors and metabolic risk factors and the presence of MetS in adults with obesity.

Methods: In a cross-sectional study of 288 apparently healthy adults with obesity aged 20-50 years, dietary glycemic index (GI) and glycemic load (GL) were measured using a validated semi-quantitative food frequency questionnaire (FFQ). Biochemical parameters, blood pressure and anthropometric indicators were assayed by standard methods. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Structural equation modeling (SEM) was used in the statistical analysis.

Results: CARTPT rs2239670 had a positive direct effect on MetS (B = 0.037 ± 0.022; P = 0.043) and, on the other hand, this variant was found to be indirectly associated with MetS presence through mediation of GI (B = 0.039 ± 0.017; P = 0.009). CARTPT was a significant predictor of both dietary GI and GL (B = 1.647 ± 0.080 and B = 3.339 ± 0.242, respectively). Additionally, glycemic indicators appeared to mediate the association of age and gender with LDL-C (B = 0.917 ± 0.332; P = 0.006) and HDL (B = 1.047 ± 0.484; P = 0.031), respectively. GI showed a positive relationship with LDL-C (P = 0.024) in men and similar relationships were found between GL and LDL-C (P = 0.050) and cholesterol (P = 0.022) levels in women.

Conclusion: The SEM findings suggest a hypothesis of the mediating effect of glycemic indices in the relationship between genetic susceptibility to obesity and MetS presence. Our findings need to be confirmed with large prospective studies.

Keywords: Glycemic index; Glycemic load; Metabolic syndrome; Obesity; Structural equation modeling.

Fig. 1

Hypothesized models in which GI and GL as mediating variables relate CARTPT rs2239670 polymorphism, socio-demographic and psychological parameters to serum lipids. Abbreviations: CART, cocaine- and amphetamine-regulated transcript; GI, glycemic index; GL, glycemic load; SES, socio-economic status; PA, Physical activity; Appe, appetite; LDL-C, low density lipoprotein cholesterol; HDL, high-density lipoprotein; TG, triglyceride; Chol, cholesterol.

Fig. 2

Hypothesized models in which GI and GL as mediating variables relate CARTPT rs2239670 polymorphism, socio-demographic and psychological parameters to serum glycemic levels. Abbreviations: CART, cocaine- and amphetamine-regulated transcript; GI, glycemic index; GL, glycemic load; SES, socio-economic status; PA, Physical activity; Appe, appetite.

Fig. 3

Hypothesized models in which GI and GL as mediating variables relate CARTPT rs2239670 polymorphism, socio-demographic and psychological parameters to MetS. Abbreviations: CART, cocaine- and amphetamine-regulated transcript; GI, glycemic index; GL, glycemic load; SES, socio-economic status; PA, Physical activity; Appe, appetite; MetS, metabolic syndrome.

Fig. 4

Path analysis diagram with standardized estimates illustrating the total effects of CARTPT rs2239670 polymorphism, diet, socio-demographic and psychological parameters on lipid profile among adults with obesity. Abbreviations: CART, cocaine- and amphetamine-regulated transcript; GI, glycemic index; GL, glycemic load; SES, socio-economic status; PA, Physical activity; Appe, appetite; LDL-C, low density lipoprotein cholesterol; HDL, high-density lipoprotein; TG, triglyceride; Chol, cholesterol.*All path coefficients are standardized. Red arrows mean p.value ≤0.05. £Total effect is defined as the sum of direct and indirect effects.

Fig. 5

Path analysis diagram with standardized estimates illustrating the total effects of CARTPT rs2239670 polymorphism, diet, socio-demographic and psychological parameters on serum glycemic levels among adults with obesity. Abbreviations: CART, cocaine- and amphetamine-regulated transcript; GI, glycemic index; GL, glycemic load; SES, socio-economic status; PA, Physical activity; Appe, appetite *All path coefficients are standardized. Red arrows mean p.value ≤0.05. £Total effect is defined as the sum of direct and indirect effects

Fig. 6

Structural equation model diagram with standardised estimates for total effects of genetic, socio-demographic and psychological parameters and diet on metabolic syndrome among adults with obesity. Abbreviations: CART, cocaine- and amphetamine-regulated transcript; GI, glycemic index; GL, glycemic load; SES, socio-economic status; MetS, metabolic syndrome; PA, Physical activity; Appe, appetite. *All path coefficients are standardized. Red arrows mean p.value ≤0.05. ^£Total effect is defined as the sum of direct and indirect effects