Association between Leptin gene polymorphisms and plasma leptin level in three consanguineous families with obesity

Abstract Introduction Leptin ( LEP ) gene is one of the most promising candidate genes for obesity. Previous studies have tested the association of polymorphisms in LEP gene with obesity and obesity-related metabolic biomarkers (anthropometric variables, glucose, insulin level, leptin level and lipid profile). However, the results of these studies were still controversial. To determine whether LEP gene is associated with obesity in Tunisian population, we performed a family-based association study between LEP polymorphisms and obesity and obesity-related metabolic biomarkers. Methods Seven single nucleotide polymorphisms (SNPs) in 5′ region of LEP gene were genotyped in three consanguineous families including 33 individuals. The previously reported LEP SNPs (H1328084, H1328082, rs10487506, H1328081, H1328080, G-2548A and A19G) were evaluated by PCR-RFLP and direct sequencing methods. Single SNP association and haplotype association analyses were performed using the family-based association test (FBAT). To determine allele frequencies of these SNPs in general population, 52 unrelated individuals from the general Tunisian population were also analyzed. Results Two SNPs showed significant associations with plasma leptin level (H1328084: A > G, Z = 2.058, p  = 0.039; A19G: G > A, Z = 2.058, p  = 0.039). When haplotypes were constructed with these two-markers, the risk AA haplotype (frequency 57.1%) was positively associated with plasma leptin level (Z = 2.058, p  = 0.039). Moreover, SNPs H1328084 and A19G are predicted to modify transcription-factor binding sites. Conclusions Our study provided that two functional variants in 5′ regulatory region of LEP gene are associated with plasma leptin level as a quantitative trait. It suggested that H1328084 and A19G have an important role in regulating plasma leptin level.