Haplotyping strategy highlights the specificity of FTO gene association with polycystic ovary syndrome in Tunisian women population

• We genotyped 4 genetic markers (SNPs) in the FTO (fat mass and obesity associated) gene in a women population from Tunisia with polycystic ovary syndrome (PCOS).
• We reconstructed the haplotypes resulting from the combination of these SNPs.
• We tested the association of SNPs and haplotypes with PCOS and its components.
• We observed association of haplotypes with PCOS stronger than was the association of SNPs taken alone.
• We attested that haplotypes are more appropriate markers for PCOS in our Tunisian population.

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 (r2 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.