title: Association between Leptin gene polymorphisms and plasma leptin level in three consanguineous families with obesity.
abstract: BACKGROUND
  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.
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine, University of Sfax, Tunisia. mounafourati@gmail.com
authors.forename: Mouna
authors.initials: M
authors.lastname: Fourati
authors.forename: Mouna
authors.initials: M
authors.lastname: Mnif
authors.forename: Najla
authors.initials: N
authors.lastname: Kharrat
authors.forename: Nédia
authors.initials: N
authors.lastname: Charfi
authors.forename: Mahdi
authors.initials: M
authors.lastname: Kammoun
authors.forename: Nourhène
authors.initials: N
authors.lastname: Fendri
authors.forename: Salwa
authors.initials: S
authors.lastname: Sessi
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abid
authors.forename: Ahmed
authors.initials: A
authors.lastname: Rebai
authors.forename: Faiza
authors.initials: F
authors.lastname: Fakhfakh
mesh_terms: D020121:5' Untranslated Regions; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003241:Consanguinity; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D020738:Leptin / Q000097:blood / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D020121:5' Untranslated Regions; D020738:Leptin
keywords: Association study; FBAT; LEP gene; Leptin gene; Obesity; Plasma leptin level; Polymorphism; SNP; TFBS; family-based association test; single nucleotide polymorphism; transcription factor binding sites