Background: The leptin receptor (LEPR) is an important regulator of leptin activity and resistance. Several single nucleotide polymorphisms (SNP) of LEPR have been linked to diseases accompanying obesity and/or obesity-related diseases in different populations. However, the results from published studies remain inconsistent rather than conclusive.
Aim: To investigate whether LEPR SNP are associated with essential hypertension and related metabolic traits in Chinese subjects.
Materials and methods: A total of 544 Chinese patients with hypertension and 357 non-hypertensive subjects were screened. The genotypes of LEPR polymorphisms were determined by PCR-restriction fragment length polymorphism methods. Demographic and biochemical characteristics including waist circumference, waist-to-hip ratio, body mass index (BMI), lipids profiles, glucose metabolism, and leptin levels were obtained for analysis.
Results: This case-control study showed associations between the frequencies of AA genotype and A allele of Gln223Arg and hypertension (p=0.029, p=0.002, respectively). Furthermore, the Gln223Arg polymorphism was significantly associated with plasma leptin levels (p<0.001), while no correlations between Lys109Arg SNP and hypertension were found. Multivariate logistic regression analysis evidenced that A allele carriers of Gln223Arg (AA+AG) showed higher risks of hypertension than GG carriers after adjustment of age and sex (adjusted odds ratio: 1.549, 95% confidence interval: 1.031- 2.036, p=0.035). BMI, fasting serum insulin, oral glucose tolernace test (OGTT)-2h glucose, serum leptin, as well as LDL-cholesterol (LDL-C) levels were also independent risk factors of hypertension in this population. In addition, significant associations were observed between the Gln223Arg and Lys109Arg SNP and serum total cholesterol, LDL-C, and fasting plasma glucose levels in hypertensive patients. Besides, A allele of Gln223Arg had raised diastolic blood pressure, compared with GG carriers (p=0.001). While variance of Lys109Arg was associated with waist-to-hip ratio, OGTT-2h glucose, and homeostasis model assessment of insulin resistance (p<0.05).
Conclusions: LEPR polymorphisms may be a marker for susceptibility to essential hypertension in Chinese subjects, and be involved in the development of several features including dyslipidemia and impaired glucose regulation in hypertension subjects.