Single Nucleotide Polymorphisms in PEMT and MTHFR Genes are Associated with Omega 3 and 6 Fatty Acid Levels in the Red Blood Cells of Children with Obesity

Abstract

Polyunsaturated fatty acids (PUFAs) play important roles in health and disease. PUFA levels are influenced by nutrition and genetic factors. The relationship between PUFA composition in red blood cells (RBCs) and genetic variations involved in PUFA metabolism has not been investigated in children with obesity. This study evaluated the association between several genetic variations and PUFA levels in RBCs in children with obesity. One hundred ninety-six children with obesity (101 females, 95 males) were evaluated using anthropometric measurements, dietary intakes, plasma and RBC PUFA quantification, blood biochemistry, and 55 single nucleotide polymorphisms within 14 genes. phosphatidylethanolamine N-methyltransferase (PEMT) rs1109859 and methylenetetrahydrofolate reductase gene (MTHFR) rs4846052 genotypes were associated with PUFA levels in RBCs. PUFA intake did not influence the RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels. Higher RBC DHA and EPA levels were observed for PEMT rs1109859 GG and GA genotypes versus the AA genotype. Higher levels of RBC DHA, EPA, arachidonic acid (ARA), and linoleic acid (LA) and were observed for MTHFR rs4846052 TT genotype versus TC and CC genotypes. Genetic variations in PEMT rs1109859 and MTHFR rs4846052 were associated with different PUFA levels in RBC membranes and are estimators for PUFA species in RBCs. Further research is needed to establish whether these genotype-specific alterations are specific to overweight children.

The Link between Homocysteine and Omega-3 Polyunsaturated Fatty Acid: Critical Appraisal and Future Directions

“…As a consequence, DHA in plasma PC has been proposed as a potential marker for PEMT activity [97]. In a study of 200 obese children, the composition of PUFAs in the PC of membrane phospholipids of red blood cells showed a lower abundance of EPA and DHA in the presence of single nucleotide polymorphisms borne by the PEMT gene [98]. This phenomenon suggests that the activity of PEMT is intimately linked to the incorporation of specific PUFAs into the PC.…”

<p><em>CHDH-PNPLA3</em> Gene–Gene Interactions Predict Insulin Resistance in Children with Obesity</p>

“…Clinical evaluation was performed in a paediatric hospital in Timisoara, Romania. Exclusion criteria were previously described elsewhere 16 and included diagnosis of cancer, or medical history of cancer; auto-immune disease; psychiatric disorder; blood coagulation disorders; history of drug abuse; familial hypercholesterolemia; endocrine-induced obesity, hypothalamusinduced obesity, genetic syndromes; deposition diseases; personal history for: convulsive disorders, nephrotic syndrome, or asthma that required corticoid treatment. Subjects with incomplete sequencing data (1 SNP missing) were excluded from this study (n=47).…”

“…Anthropometric measurements were performed following international guidelines, 17 as described previously. 16 Standardized BMI-for-age z-scores (zBMI) were calculated according to the World Health Organization guidelines taking into account the age and gender of the child. 15 Waist circumference was measured with an inextensible anthropometric tape, by a trained person, to the nearest 0.1 cm, in standing position, at the midpoint between the end of the rib cage and the top of the iliac crest.…”

“…Total plasma concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and glucose were performed using its standardized reagents and following the manufacturer's protocols, as presented previously. 16 Insulin measurements were performed using ELISA method, as shown. 16 Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated using the formula: fasting insulin (mIU/L) × fasting glucose (mmol/L)/22.5.…”

“…16 Insulin measurements were performed using ELISA method, as shown. 16 Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated using the formula: fasting insulin (mIU/L) × fasting glucose (mmol/L)/22.5. In order to account for differences between boys and girls and for the physiological insulin resistance during puberty, 21 different HOMA-IR cut-offs were used to define insulin resistance, stratified by gender and by age groups.…”