List of Publications by Department for the Academic Year Gene Polymorphism in the Hormone Binding Site of Leptin Receptor in Obese Diabetic Patients in Lebanon
Abstract
Introduction Leptin hormone is produced by the adipocytes, and is known to act as a satiety factor through binding to its receptors in the hypothalamus in the brain. Leptin receptor binds to its ligand through five amino acids (I F L L S) in the CRH2 domain. These amino acids are encoded by 15 nucleotides in exon 12 sequence in the LEPR gene (NG_015831.2). It is suggested that polymorphisms in the leptin receptor gene may lead to obesity and type 2 diabetes mellitus. The presence of polymorphisms in these nucleotides in obese and diabetic patients have not been studied before. Objectives This study investigated whether there is a polymorphism in the nucleotides coding for the I F L L S amino acids in the CRH2 domain in exon 12 or any polymorphism in the region from 189481 to 189905 sequence in the leptin receptor gene in the Lebanese population. Materials and methods 80 Lebanese subjects: 20 lean/non-diabetic control subjects, 20 obese/non-diabetic subjects, 20 obese/diabetic subjects, and 20 lean/diabetic subjects were recruited. Genomic DNA was isolated from whole blood and amplified by PCR followed by purification and sequencing. Weight and height were measured to calculate the BMI of the participants. Fasting plasma glucose levels were also measured. Results No polymorphisms were found in the nucleotides coding for the I F L L S amino acids in the CRH2 domain in exon 12. A new T/A polymorphism at nucleotide 189835 in the LEPR gene was found with 3 genotypes: TT, TA, and AA. This polymorphism was not identified before and we termed it rs 189835. No statistically significant variation in the genotype frequencies distributions of this polymorphism (P>0.05) between obese/non-diabetic and control subjects was found. When comparing both obese/diabetic and lean/diabetic subjects with control subjects significant variation was observed. Interestingly, the AA genotype was found in the non-diabetic subjects and not in diabetic patients. No significant association with BMI and fasting plasma glucose levels was observed for the SNP rs 189835. Conclusion According to these observations, it is suggested that this polymorphism has no significant association with obesity in the Lebanese population. However, the AA genotype may have a protective role against the incidence of diabetes.
Author(s)
Natalie Hassan Hissi
Coauthor(s)
Pof. Mohamad Sayed Moustafa, Prof. Mahmoud Balbaa