Association of leptin/receptor and TNF-α gene variants with adolescent obesity in Malaysia

Pediatr Int. 2014 Oct;56(5):689-97. doi: 10.1111/ped.12336. Epub 2014 Jun 17.


Background: Leptin (LEP) G-2548A (rs7799039), leptin receptor (LEPR) Q223R (rs1137101) and tumor necrosis factor (TNF)-α G-308A (rs1800629) gene variants have been reported to be associated with obesity, although results for subjects from different countries have been controversial. The aim of this study was to determine the prevalence of overweight and obesity in Malaysian adolescents and the association of these polymorphisms with overweight and obese or over-fat adolescents.

Methods: A total of 613 adolescents (241 Malay, 219 Chinese, 153 Indian) were enrolled. Anthropometric measurements of body mass index (BMI) and body fat percentage were used to classify subjects as controls (non-overweight/obese or normal fat) or as cases (overweight/obese or over-fat). Genomic DNA was extracted from oral buccal mucosa cells for genotyping using polymerase chain reaction-restriction fragment length polymorphism and data obtained were statistically analyzed.

Results: A total of 23.3% of subjects were overweight/obese whereas 11.4% were over-fat; there were significantly more overweight/obese and over-fat Indian and Malay adolescents compared to Chinese (P < 0.001). A allele was the minor one for LEPR Q223R and TNF-α G-308A in all ethnic groups, whereas G allele was minor for LEP G-2548A in Chinese and Malay adolescents, except for Indian adolescents. Indian male adolescents with AA genotype for LEP G-2548A were associated with overweight/obesity (P = 0.025; odds ratio, 3.64; 95% confidence interval: 1.15-11.54). Despite the lack of association observed for LEPR Q223R and TNF-α G-308A, Indian and Chinese subjects with AA risk genotype for LEPR Q223R/LEP G-2548A and TNF-α G-308A/LEP G-2548A, respectively, had increased mean BMI (P = 0.049, P = 0.016).

Conclusions: Genotype distribution and association of these polymorphisms with overweight/obesity vary between ethnic groups and genders. Nevertheless, the LEP G-2548A risk allele may be associated with overweight/obese Indian male adolescents in Malaysia.

Keywords: adolescents; body fat percentage; body mass index; leptin; leptin receptor; single nucleotide polymorphism; tumor necrosis factor-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Female
  • Genetic Variation
  • Humans
  • Leptin / genetics*
  • Malaysia / epidemiology
  • Male
  • Overweight / epidemiology
  • Overweight / genetics
  • Pediatric Obesity / epidemiology*
  • Pediatric Obesity / genetics*
  • Prevalence
  • Receptors, Leptin / genetics*
  • Tumor Necrosis Factor-alpha / genetics*


  • Leptin
  • Receptors, Leptin
  • Tumor Necrosis Factor-alpha