title: Haplotyping strategy highlights the specificity of FTO gene association with polycystic ovary syndrome in Tunisian women population.
abstract: The FTO (fat mass and obesity associated) gene was associated with different metabolic disorders in populations from different origins but with great difference between African and non-African populations. North-African populations combine many genetic backgrounds, among which African, Berber and Caucasian components, which makes North-Africans a good model for studying the genetic association of FTO. In the present investigation we explored the association of FTO gene with polycystic ovary syndrome (PCOS) in a population from Tunisia (n=278). Single nucleotide polymorphisms (SNPs) used in this study were previously associated in non-African populations: rs8050136 (A/C), rs9939609 (A/T), rs9930506 (G/A), or in both African and non-African populations: rs8057044 (A/G). Genotyping was performed by allelic discrimination method on StepOne real-time PCR system or KASPar technology. Linkage disequilibrium (LD) pattern was assessed by HAPLOVIEW and reconstruction of haplotypes was performed by PHASE, while statistical analyses were performed using StatView and GoldenHelix programs. Among the 13 haplotypes in the population, three (h1, h7 and h13) were strongly associated with PCOS notably h13 (P<0.0001, OR95%CI=0.040 [0.005-0.294]) while SNPs display weaker association. Moreover the LD pattern in FTO in the Tunisian population (r(2) index) was intermediary between those of Caucasian and Africans. This highlights the need for studying the genetics of complex disorders in the North-African populations taking into-account the haplotype structure of candidate loci more than SNPs taken alone.
authors.affiliation: Laboratory of Human Genome and multifactorial diseases, LR12ES07, Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia.
authors.forename: Assila
authors.initials: A
authors.lastname: Ben Salem
authors.affiliation: IURC, Molecular Endocrinology Laboratory, Nutrition & Genomes, UMR-204, NUTRIPASS, Montpellier, France.
authors.forename: Redha
authors.initials: R
authors.lastname: Attaoua
authors.affiliation: Laboratory of Human Genome and multifactorial diseases, LR12ES07, Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia.
authors.forename: Nabil
authors.initials: N
authors.lastname: Mtiraoui
authors.affiliation: University Hospital F. Hached, Unit of Reproductive Medicine, Sousse, Tunisia.
authors.forename: Sawssen
authors.initials: S
authors.lastname: Meddeb
authors.affiliation: University Hospital F. Hached, Unit of Reproductive Medicine, Sousse, Tunisia.
authors.forename: Olfa
authors.initials: O
authors.lastname: Kacem
authors.affiliation: University Hospital F. Hached, Unit of Reproductive Medicine, Sousse, Tunisia.
authors.forename: Mounir
authors.initials: M
authors.lastname: Ajina
authors.affiliation: Department of Obstetrics and Gynaecology, CHU Tahar Sfar, Mahdia, Tunisia.
authors.forename: Moncef
authors.initials: M
authors.lastname: Souissi
authors.affiliation: Pharmacology and Experimental Physiology Laboratory, Faculty of Pharmacy, Montpellier, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Poucheret
authors.affiliation: IURC, Molecular Endocrinology Laboratory, Nutrition & Genomes, UMR-204, NUTRIPASS, Montpellier, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Normand
authors.affiliation: Laboratory of Human Genome and multifactorial diseases, LR12ES07, Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia.
authors.forename: Touhami
authors.initials: T
authors.lastname: Mahjoub
authors.affiliation: IURC, Molecular Endocrinology Laboratory, Nutrition & Genomes, UMR-204, NUTRIPASS, Montpellier, France. Electronic address: florin.grigorescu@inserm.fr.
authors.forename: Florin
authors.initials: F
authors.lastname: Grigorescu
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D014416:Tunisia; D044465:White People / Q000235:genetics
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human
keywords: Genetic association; Linkage disequilibrium; North-Africans; Polycystic ovary syndrome