@article{fdi:010075517,
  title = {{F}ine-scale haplotype mapping of {MUT}, {AACS}, {SLC}6{A}15 and {PRKCA} genes indicates association with insulin resistance of metabolic syndrome and relationship with branched chain amino acid metabolism or regulation},
  author = {{H}aydar, {S}. and {G}rigorescu, {F}lorin and {V}intila, {M}. and {C}ogne, {Y}. and {L}autier, {C}. and {T}utuncu, {Y}. and {B}run, {J}. {F}. and {R}obine, {J}. {M}. and {P}ugeat, {M}. and {N}ormand, {C}. and {P}oucheret, {P}. and {G}heorghiu, {M}. {L}. and {G}eorgescu, {C}. and {B}adiu, {C}. and {B}aculescu, {N}. and {R}enard, {E}. and {Y}lli, {D}. and {B}adiou, {S}. and {S}utra, {T}. and {C}ristol, {J}. {P}. and {M}ercier, {J}. and {G}omis, {R}. and {M}acias, {J}. {M}. and {L}itvinov, {S}. and {K}husnutdinova, {E}. and {P}oiana, {C}. and {P}asquali, {R}. and {L}auro, {D}. and {S}esti, {G}. and {P}rudente, {S}. and {T}rischitta, {V}. and {T}satsoulis, {A}. and {A}bdelhak, {S}. and {B}arakat, {A}. and {Z}enati, {A}. and {Y}lli, {A}. and {S}atman, {I}. and {K}anninen, {T}. and {R}inato, {Y}. and {M}issoni, {S}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ranched chain amino acids ({BCAA}) are essential elements of the human diet, which display increased plasma levels in obesity and regained particular interest as potential bio-markers for development of diabetes. {T}o define determinants of insulin resistance ({IR}) we investigated 73 genes involved in {BCAA} metabolism or regulation by fine-scale haplotype mapping in two {E}uropean populations with metabolic syndrome. {F}rench and {R}omanians (n = 465) were genotyped for {SNP}s ({A}ffymetrix) and enriched by imputation ({BEAGLE} 4.1) at 1000 genome project density. {I}nitial association hits detected by sliding window were refined ({HAPLOVIEW} 3.1 and {PHASE} 2.1) and correlated to homeostasis model assessment ({HOMA}({IR})) index, in vivo insulin sensitivity ({S}-{I}) and {BCAA} plasma levels ({ANOVA}). {F}our genomic regions were associated with {IR} located downstream of {MUT}, {AACS}, {SLC}6{A}15 and {PRKCA} genes ({P} between 9.3 and 3.7 x 10(-5)). {I}nferred haplotypes up to 13 {SNP}s length were associated with {IR} (e.g. {MUT}gene with {P} < 4.9 x 10(-5); {B}onferroni 1.3 x 10(-3)) and synergistic to {HOMA}({IR}). {SNP}s in the same regions were also associated with one order of magnitude lower {P} values (e.g. rs20167284 in the {MUT} gene with {P} < 1.27 x 10(-4)) and replicated in {M}editerranean samples (n = 832). {I}n {F}rench, influential haplotypes ({OR} > 2.0) were correlated with in vivo insulin sensitivity (1/{S}-{I}) except for {SLC}6{A}15 gene. {A}ssociation of these genes with {BCAA} levels was variable, but influential haplotypes confirmed implication of {MUT}from {BCAA} metabolism as well as a role of regulatory genes ({AACS} and {PRKCA}) and suggested potential changes in transcriptional activity. {T}hese data drive attention towards new regulatory regions involved in {IR} in relation with {BCAA} and show the ability of haplotypes in phased {DNA} to detect signals complimentary to {SNP}s, which may be useful in designing genetic markers for clinical applications in ethnic populations.},
  keywords = {{FRANCE} ; {ROUMANIE}},
  booktitle = {},
  journal = {{PL}o{S} {O}ne},
  volume = {14},
  numero = {3},
  pages = {e0214122 [23 p.]},
  ISSN = {1932-6203},
  year = {2019},
  DOI = {10.1371/journal.pone.0214122},
  URL = {https://www.documentation.ird.fr/hor/fdi:010075517},
}