Polymorphisms in the 3′UTR of the human leptin gene and their role in hypertension

Leptin is a protein hormone, mainly synthesized in adipocytes, that regulates the food intake and energy expenditure of the body. Rare mutations in the leptin gene cause obesity. Common polymorphisms of the leptin gene have been associated with obesity, however their association with arterial blood pressure has not been fully elucidated. The aim of the present study was to examine the effect of variants in the 3′ flanking region of the leptin gene on blood pressure in hypertensive subjects with high (35.2±5.12) and low (20.13±1.3) body mass index (BMI). Microsatellite polymorphisms and the C538T SNP in the 3′UTR of the leptin gene were screened in 362 subjects, and different biochemical and anthropometric parameters were measured. The levels of serum urea, creatinine, glucose, cholesterol, triglyceride, leptin and angiotensin II were determined in all subjects. A strong association of microsatellite polymorphisms with essential hypertension was found in subjects with a high BMI, but this association was only slight in subjects with a normal BMI. The C538T variant was not found in this population. The frequency of the Class I/Class I and Class I/Class II genotype for tetranucleotide polymorphisms was also significantly higher in the hypertensive compared to the normotensive group (p≤0.0001). In addition, a significant correlation was found between serum leptin and Class I/I and Class I/II genotypes. Linear regression analysis showed an independent correlation of leptinemia with BMI (p=0.019), while a notable correlation was found between serum leptin concentration and angiotensin II. The study confirmed that shorter alleles of microsatellites in the 3′ flanking region of leptin are significantly associated with hypertension, however, the underlying mechanism remains unknown.