Association between LEPR, FTO, MC4R, and PPARG-2 polymorphisms with obesity traits and metabolic phenotypes in school-aged children

Abstract

PurposeEvaluate the relationship of leptin receptor (LEPR) rs1137101, fat mass obesity-associated (FTO) receptors 9939609, melanocortin-4 receptors (MC4R) rs2229616 and rs17782313, and proliferator-activated receptor-gamma (PPARG) rs1801282 with clinical and metabolic phenotypes in prepubertal children.Research questionWhat is the effect of polymorphisms on clinical and metabolic phenotypes in prepubertal children?MethodsA cross-sectional descriptive study was performed to evaluate anthropometric features, percentage body fat (%BF), biochemical parameters, and genotype in 773 prepubertal children.ResultsFTO rs9939609 was associated with an increase in body mass index (BMI) and BMI z-score (zBMI). MC4R rs17782313 was associated with a decrease in BMI and +0.06 units in zBMI. LEPR, and PPARG-2 polymorphisms were associated with decreases in BMI and an increase and decrease units in zBMI, respectively. The homozygous SNPs demonstrated increases (FTO rs993609 and MC4R rs17782313) and decreases (LEPR rs1137101, PPARG rs1801282) in zBMI than the homozygous form of the major allele. In the overweight/obese group, the MC4R rs17782313 CC genotype showed higher average weight, zBMI, waist circumference, waist-circumference-to-height ratio, and waist-hip ratio, and lower BMI, mid-upper arm circumference, calf circumference, and %BF (P< 0.05). FTO rs9939609 AT and AA genotypes were associated with lower triglycerides (P < 0.05).ConclusionsWe showed that MC4R rs17782313 and FTO rs9939609 were positively associated with zBMI, with weak and very weak effects, respectively, suggesting a very scarce contribution to childhood obesity. LEPR rs1137101 and PPARG-2 rs1801282 had weak and medium negative effects on zBMI, respectively, and may slightly protect against childhood obesity.

Targeted sequencing analysis of PPARG identifies a risk variant associated with obstructive sleep apnea in Chinese Han subjects

“…Obesity plays an important role in OSA. PPARG rs1801282 polymorphisms were associated with decreased BMI and may slightly protect against childhood obesity [39]. BMI is associated with PPARG and adipogenesis is affected by PPARG [19], a known regulator of lipid and glucose metabolism.…”

The Q223R Polymorphism of the Leptin Receptor Gene as a Predictor of Weight Gain in Childhood Obesity and the Identification of Possible Factors Involved

“…However, the functional outcomes for this genetic variant remain poorly defined [29]. The existence of contradictory results [30,31] may be explained either by the gender influence [32] or the underpowered available studies [33].…”

Polimorfismos de los genes del sistema leptina-melanocortina asociados con la obesidad en la población adulta de Barranquilla

“…Lo mismo sucede con el polimorfismo rs17782313 del gen MC4R , el cual se ha asociado con un elevado IMC ( 8 , 28 , ( 29 ) y con la aparición temprana de obesidad grave 9 . Se ha sugerido que los portadores del genotipo TT de este polimorfismo tienen un nivel notablemente mayor de hipermetilación en el promotor de MC4R en comparación con los portadores de los genotipos CT y CC, lo que puede contribuir a regular la expresión de MC4R y, por consiguiente, al desarrollo de la obesidad 30 .…”