Life Sci J.2012 9(4):818-828

Impact of Leptin Receptor Gene GLN223ARG Polymorphism on Obesity in Jeddah City

Sabah A. Linjawi and Noor A. Hussain

Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia, slinjawi@kau.edu.sa

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Abstract:

     Obesity is a major global epidemic problem. Obesity is a complex disorder resulting from a net imbalance between genetic, energy intake and expenditure. Obesity results from the combined effects of genes, lifestyle and the interactions of these factors. The leptin receptor gene plays a critical role in the regulation of body weight. Genetic variations of leptin receptor gene may play a role in the pathophysiology of human obesity.

      In this study we investigated the distribution of alleles of the leptin receptor GLN223ARG polymorphism in 180 volunteers (94 male & 86 female) from Jeddah population and the association with the obesity prevalence. Each gender was divided into two groups: from 6-17 years old (Children and Teenager), and from 18-27 years old (Adults). As well as each group were divided into two sub-groups according to BMI (obese and non obese “control”).

     When comparison the obese and non obese groups, results demonstrated that no significant difference between genotype distribution and body mass index (BMI), weight, hip, waist and waist-hip ratio (WHR). In contrast, there was a significant increase in GG genotype (OR= 19.11, 95%CI: 0.95-384.95, P= 0.01) compared to AA genotype, and GG genotype (OR= 25.24, 95%CI: 1.25-509.46, P= 0.006) compared to AG genotype in males children and teenagers, which suggests that leptin receptor gene may play a role in this group obesity.

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Supplement:

Why we study the obesity in Jeddah city?

Obesity has occupied a prominent place in the health concerns of physicians, due to being related to many chronic diseases such as heart disease, diabetes and others. So, we regard it as a must as a scientific researcher to investigate and highlight the obesity main genetic causes specially in Jeddah city, and provide a necessary awareness cautions to avoid obesity, aiming to protect our generations from obesity diseases. Obesity is the most common nutritional problem in Kingdom of Saudi Arabia (KSA). Previous studies in KSA conducted, have shown an increase overall prevalence of obesity. This indicates that health authorities need to address the problem in KSA. Childhood obesity increases the risk of obesity in adulthood. Whitaker et al., (1997) found that obesity is an increasingly important predictor of adult obesity among older children. Moreover, overweight in adolescence predicts a broad range of adverse health effects. It is important to identify the cause of obesity, and to prevent obesity in childhood. Therefore, this study targeted the age group (6-17 years old). Due to prevalence of fast food restaurants in Jeddah, eating junk food has increased and this is surely linked to obesity. Numerous studies found  associations between fast food intake and increased BMI and weight gain.

What is the role of Leptin in regulation of body weight ?

Sabah Linjawi-1Figure 1: The control of food intake by the brain is an integral part of nutrition. After having a meal  the researcher observes an increasing level of lipids in Adipocytes and hence increases the size of this cells, the rising level of lipid leads to the secretion of the leptin , which in turn moves and passes the blood-brain barrier and up to the receptors in the Hypothalamic Arcuate Nucleus (ARC). the association with receptors  leads to inhibition of both neuropeptide Y (NPY), agouti-related protein (AGRP) which is Appetite stimulating, finally person stops  eating and feeling of satiety.

The genotype and allele frequencies of GLN223ARG polymorphism in children and teenagers males group (6-17 years old) show that, when comparing the obese and control groups results, the frequency of the homozygote GG were highly significant (P= 0.006) because there was no GG genotype in control group. There was an increased frequency of the A allele in control group (72.9) compared to obese group (59.1) and an increased frequency of the G allele in obese group (40.9) compared to control group (27.1). When comparing AA and AG genotype the odd ratio (OR) was (0.75), this indicated there were no effect and association. When comparing between AA and GG genotype (P= 0.01) the odd ratio was (19.11), which indicated that the odds of obese is about 19 times higher in GG genotype compared to control (RR=12.47, 95% CI: 0.75-207.2). When comparing between AG and GG genotype (P= 0.006) the odd ratio was (25.24), indicated that the odds of obese are about 25-fold higher in GG genotype than control (RR=15.71, 95% CI: 0.94-261.9) (Figure 2).

Sabah Linjawi-2Figure  2: The frequency distribution of GLN223ARG genotypes in children and teenagers males (6-17 years old).

The comparison results between all obese children and teenagers (males and females) and all obese adults (males and females) indicated an increased frequency of the GG genotype in obese children and teenagers (4 times) than obese adults, and an increased frequency of the AA and AG genotype in obese adults (Figure 3).

Sabah Linjawi-3Figure  3: The frequency distribution of GLN223ARG genotypes in all all obese children and teenagers and adults

Also the comparison results between obese males and females, demonstrated an increased frequency of the AA and GG genotype in obese females and an increased frequency of the AG genotype in obese males (Figure 4).

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 Sabah Linjawi-4Figure 4:  The frequency distribution of GLN223ARG genotypes in all obese males and females.

Conclusion: Based on the results of this study, there was a significant association in males children and teenager groups with too high risks may be due to overweight and obesity in this groups.

Reference:

Whitaker, R. C., Wright, J. A., Pepe, M. S.,Seidel, K. D., Dietz, W.H. (1997): Predicting obesity in young adulthood from childhood and parental obesity. New Engl J Med, 337, p. 869-873

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