Lys656Asn polymorphism of leptin receptor, leptin levels and insulin resistance in patients with non alcoholic fatty liver disease

R. Aller 1, D.A. de Luis 2, O. Izaola 2, M. González Sagrado 2, R. Conde 2, D. Pacheco 2, M.C. Velasco 2, H.F. Ovalle 2

¹ Department of Gastroenterology, Hospital Clínico Universitario de Valladolid (Spain)
² Center of Investigation of Endocrinology and Clinical Nutrition, Medicine School and Unit of Investigation, Hospital Rio Hortega, Valladolid University, Valladolid (Spain)

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• Internal Medicine

Background: Some studies have pointed to a role of leptin and insulin resistance in pathogenesis of non alcoholic fatty liver disease (NAFLD). The aim of our study was to investigate the influence of Lys656Asn polymorphism LEPR gene on the histological changes, insulin resistance and leptin levels in overweight patients.

Material and Methods: A population of 76 patients with NAFLD was recruited in a cross sectional study. A biochemical analysis of serum was measured. Genotype of LEPR gene Lys656Asn was studied.

Results: Nineteen patients (25%) had the genotype Lys656Asn and 4 patients genotype Asn656Asn (mutant type group) and 53 patients (69.7%) Lys656Lys (wild type group). Body mass index, weight, fat mass, waist circumference, waist to hip ratio, glucose levels and HOMA-IR were higher in mutant than wild type group. LEPR polymorphism is in any way related with liver lesions. The multivariate analysis adjusted by age, sex, BMI and genotype showed an independently association of lobular inflammation 4.19 (CI95%: 1.37-12.77), portal inflammation 1.97 (CI95%: 1.05-3.74) and steatosis 9.23 (CI95%: 1.47-57.83) with HOMA. Liver steatosis was associated with leptin levels (1.09 (CI95%: 1.06-1.18)), too.

Conclusion: Lys656Asn polymorphism of LEPR gene is associated with obesity parameters, insulin resistance and glucose levels in patients with NAFLD. In logistic regression analysis, only insulin resistance was associated with portal inflammation), lobular inflammation and steatosis; liver steatosis was related with leptin levels, too.

Corresponding Author: Daniel A. de Luis, MD; e-mail: dadluis@yahoo.es