A specific variant of the LEPR gene is associated with obesity, according to a study in Chinese adolescents of Han ethnicity.
The research, “Association study between LEPR, MC4R polymorphisms and overweight/obesity in Chinese Han adolescents,” was published in the journal Gene.
According to previous studies, overweight adolescents have a 70% likelihood of becoming overweight or obese adults, increasing the risk for hypertension, cardiovascular disease, type 2 diabetes, and certain types of cancer. The heritability of obesity is currently estimated at 40-70%.
A hormone called leptin is involved in the metabolism of fat and in suppressing food intake via its LEPR receptor. Mutations in LEP, which codes for leptin, and LEPR have been associated with obesity in humans and in mice. Also, deficiency in the LEPR gene ultimately lead to severe obesity right after birth, although recent research showed gender differences.
In addition, genome-wide association studies — which assess DNA to find genetic variations associated with a particular disease — reported the association between single nucleotide polymorphisms (SNPs, differences in a single nucleotide, the building blocks of DNA) within or near the MC4R gene and obesity. According to a 2001 study, mutations in MC4R, a gene with a key role in body weight regulation, are the most common single gene cause of obesity.
Given the lack of studies on obesity in adolescents of Chinese Han ethnicity (the most common in China), a team from Shanghai Jiao Tong University and Fudan University explored the role of frequent polymorphisms (gene variants) of LEPR — namely rs1137100 and rs8179183 — and MC4R — rs17782313, rs10871777, rs12970134, and rs17700144 — in obesity.
A total of 400 adolescents (ages 14-18, 237 boys, 163 girls), 178 of whom were overweight or obese, and 222 were healthy controls, were analyzed. All underwent genetic testing as well as physical examinations, including weight and height, body mass index (BMI), chest, waist, and hip circumference, and blood pressure.
Biochemical analysis of plasma levels of glucose, insulin, C-peptide (a measure of insulin secretion) total and HDL cholesterol, triglycerides, apolipoproteins A1 (APOA1) and B (APOB) — both implicated in lipid transport and metabolism — and leptin was also conducted.
Results revealed that chest, waist, and hip circumference, as well as systolic and diastolic blood pressure, the levels of cholesterol, triglycerides, APOB, and C-peptide were higher in obese participants than in controls.
The team found that the frequency of rs8179183, an SNP in LEPR, was significantly different between obese and healthy participants, with 5.3% more obese adolescents having a particular gene copy (the C allele) of rs8179183 compared to controls. Of note, this SNP causes a so-called missense mutation, and as a result, leptin’s function in the regulation of food intake and body temperature is impaired.
Further analysis revealed that rs8179183 was associated with serum triglyceride levels after adjusting for age and BMI. Adolescents carrying the rs8179183 GC or CC genotypes (G referring to guanine and C to cytosine, two nucleotides) had more triglycerides than GG carriers.
No other SNPs correlated with obesity.
“In summary, our results found a significant association between LEPR SNP rs8179183 and overweight/obesity in Chinese Han adolescents. We also found an association between this SNP and serum triglyceride content,” the scientists stated.
Nonetheless, the team emphasized that further genetic studies with larger sample sizes are needed, and suggested that rs8179183 “might be used as a marker for predicting the obesity in Chinese Han adolescents.”