florin grigorescu - Academia.edu (original) (raw)

Papers by florin grigorescu

Molecular Basis of Insulin Action, 1985

Biochemical and Biophysical Research Communications, 1985

To characterize the carbohydrate moieties of the insulin receptor on IM-9 lymphocytes, the cells ... more To characterize the carbohydrate moieties of the insulin receptor on IM-9 lymphocytes, the cells were surface iodinated and solubilized, and the insulin receptors were precipitated with anti-receptor antibody. The precipitates were resuspended, subjected to either enzymatic digestion or chemical treatment with trifluoromethanesulfonic acid and the relative mobilities of the alpha and beta subunits before and after treatment were analyzed by polyacrylamide gel electrophoresis and autoradiography. The results indicate that the alpha subunit possesses primarily N-linked carbohydrate which is both complex (Endoglycosidase F sensitive) and polymannose (Endoglycosidase H sensitive). The beta subunit also contains polymannose oligosaccharide units and has, in addition, a substantial amount of carbohydrate which is removed by chemical treatment but is not susceptible to Endoglycosidase F, suggesting the presence of O-linked saccharides. The apparent molecular weights of the core protein of the mature alpha and beta subunits as determined by gel electrophoresis following complete deglycosylation are 98 kDa and 80 kDa, respectively.

Biochemical Society transactions, 1993

Diabetes & Metabolism, 2014

ABSTRACT Introduction Dans les populations méditerranéennes, le syndrome métabolique (SMet) prése... more ABSTRACT Introduction Dans les populations méditerranéennes, le syndrome métabolique (SMet) présente une variabilité du profil clinico-biologique et du risque cardiovasculaire voire de la mortalité qui lui est associée. Dans le projet Européen MEDIGENE (FP7-279171) coordonné par l’UM-1 Montpellier (France) deux gènes candidats du SMet ont été priorisés tenant compte des études de GWAS : FTO (fat mass and obesity associated gene) et CRP (C-reactive protein gene). Patients et méthodes Nous avons étudié leur association au SMet dans une population algérienne recrutée dans les régions d’Alger et de Tlemcen (n = 350) bien caractérisée sur le plan métabolique. La prévalence du SMet était de 27,2 % (selon la définition ATPIII). Le génotypage des SNP rs1421085 (T/C) et rs3091244 (C/T), marqueurs des gènes FTO et CRP, respectivement a été effectué par KASPar tandis que l’analyse statistique a été réalisée par StatView Résultats Nous avons constaté un dosage génique du FTO (génotype C/C de rs1421085) avec l’accumulation des composantes du SMet (0 % ; 11,3 % ; 24,5% ; 19,4 % et 38 % dans les groupes d’individus avec aucun, 1, 2, 3, 4 critères de SMet, respectivement). Nous avons aussi observé la corrélation du génotype CC du gène CRP avec des valeurs plus élevées de tour de taille (101,4 ± 1,1 vs 98,1 ± 1,1 cm ; P < 0,039) alors que le génotype TT corrèle avec des taux de glycémie à jeun plus faibles (1,13 ± 0,05 vs 1,31 ± 0,05 mg. dl), P < 0,039). Enfin, le génotype CC du FTO corrèle avec des niveaux de glycémie à jeun plus importants (1,41 ± 0,1 vs 1,19 ± 0,0 mg/dl, P < 0,018). Discussion Ce travail s’inscrit dans une logique de comparaison des populations immigrantes et natives en France ainsi que celles des pays d’origine afin d’identifier des modèles d’étude de la génétique du SMet basés sur la divergence phénotypique et de l’ancestralité des populations.

Annales d'endocrinologie, Jan 14, 2017

APOA5 has been linked to metabolic syndrome (MetS) or its traits in several populations. In North... more APOA5 has been linked to metabolic syndrome (MetS) or its traits in several populations. In North Africa, only the Moroccan population was investigated. Our aim is to assess the association between APOA5 gene polymorphisms with the susceptibility to MetS and its components in the Tunisian population. A total of 594 participants from the Tunisian population were genotyped for two polymorphisms rs3135506 and rs651821 located in APOA5 gene using KASPar technology. Statistical analyses were performed using R software. The SNP rs651821 increased the risk of MetS under the dominant model (OR=1.91 [1.17-3.12], P=0.008) whereas the variant rs3135506 was not associated with MetS. After stratification of the cohort following the sex, only the variant rs651821 showed a significant association with MetS among the women group. The influence of the geographic origin of the studied population on the genotype distribution of APOA5 variants showed that the variant rs651821 was significantly associat...

Human Genetics, Apr 10, 2003

In order to understand the role of the insulin receptor substrate-2 (IRS2) gene (chromosome regio... more In order to understand the role of the insulin receptor substrate-2 (IRS2) gene (chromosome region: 13q34) in obesity, a complex disorder associated with insulin resistance and glucose intolerance, we determined single nucleotide polymorphims (SNPs) and complex haplotypes in women with morbid obesity and a body mass index (BMI) of 41±0.8 kg/m 2 (n=99) compared with controls having a BMI of 23.8±0.1 kg/m 2 (n=92). Sequencing of unphased DNA or digestion of polymerase chain reaction fragments revealed seven SNPs, including a new C/T(-769) replacement at the 5' untranslated region. Considering four or seven SNPs, we reconstructed with the PHASE program nine or 24 haplotypes, respectively, that were well correlated into the cladogram. Logistic regression analysis with nine haplotypes in the whole sample revealed that obesity was associated with haplotype H3, with P<0.025, an odds ratio (OR) of 1.9 and a 95% confidence interval (CI) of 1.1-3.4, or pairs 3/3 (P<0.005, OR=8.7, CI=1.9-40.1) and 3/4 (P<0.023, OR=2.5, CI=1.1-5.6), all containing the the Gly1057Asp allelic variant of IRS2, whereas controls were associated with H5 and H6 (P<0.02, OR=0.2, CI=0.01-0.81). Although obese H5 carriers (also containing Gly1057Asp mutation) were the most insulin resistant, haplotypes of IRS2 were poorly correlated (analysis of variance) with insulin resistance. By contrast, haplotypes H3, H4 and pairs 3/3 were consistently associated with increased 2-h glucose levels during an oral glucose tolerance test in obese individuals (P<0.0005, 0.025 and 0.027, respectively). These data indicate that IRS2 is an influential gene in severe obesity and glucose intolerance in this population, whereas gene-based haplotypes of IRS2 have revealed heterogeneity in the behaviour of the Gly1057Asp mutation in relation to insulin resistance.

Diabetes Metabolism, 2001

Reproductive BioMedicine Online, 2016

Diabetes, 1986

The type A syndrome of insulin resistance and acanthosis nigricans is characterized by severe ins... more The type A syndrome of insulin resistance and acanthosis nigricans is characterized by severe insulin resistance due to a cellular defect in insulin action. To better understand the molecular nature of this defect, we have investigated insulin binding to circulating monocytes, erythrocytes, and the Triton X-100-solubilized erythrocyte receptor, and insulin-stimulated receptor autophosphorylation using cells and receptor from three type A patients. Insulin binding in both circulating cells and the soluble extract of erythrocytes indicated a heterogeneity of defects. Patients A1 and A2 both presented a major decrease in tracer insulin binding to intact cells and soluble insulin receptor. Determination of stoichiometric binding parameters using a cooperative model indicated that in patient A1 this was due to a reduction in the number of receptors, whereas in patient A2 the affinity constant for binding was decreased. Patient A3 presented near-normal insulin binding to erythrocytes and normal binding in intact monocytes, solubilized erythrocyte receptors, and cultured fibroblasts. Affinity labeling of erythrocyte receptor from this patient revealed a normal alpha-subunit and also a normal relative distribution of the higher-molecular-weight, nonreduced oligomeric forms of the receptor. Receptor autophosphorylation was measured using the solubilized insulin receptor from erythrocytes. The maximal stimulated phosphorylation was reduced by 79%, 76%, and 52% in patients A1, A2, and A3, respectively, relative to the simultaneous control. In all three patients, the autophosphorylation was stimulated only 1.0-3.5 times the basal level compared with controls, in which the stimulation was 5.7-fold +/- 1.2 (mean +/- 1 SD, P less than 0.005). In addition, in patients A1 and A2 a decrease in basal phosphorylation was observed and in patient A2 there was a rightward shift of the dose-response curve for insulin stimulation. These data and the correlation of coupling of receptor phosphorylation with the fractional occupancy of the receptor measured in the same extract suggest that these patients exhibit three types of defects. In patient A1, there is a loss in receptor number manifested by a parallel decrease in insulin binding and receptor phosphorylation. In patient A2, there is an additional decrease in the affinity constant leading to a decrease in both binding and receptor phosphorylation with an almost linear coupling between receptor occupancy and receptor phosphorylation.(ABSTRACT TRUNCATED AT 400 WORDS)

Revue Francaise D Endocrinologie Clinique Nutrition Et Metabolisme, 1994

Approximately 10 percent of infants with intrauterine growth retardation remain small, and the ca... more Approximately 10 percent of infants with intrauterine growth retardation remain small, and the causes of their growth deficits are often unclear. We postulated that mutations in the gene for the insulin-like growth factor I receptor (IGF-IR) might underlie some cases of prenatal and postnatal growth failure. We screened two groups of children for abnormalities in the IGF-IR gene. In one group of 42 patients with unexplained intrauterine growth retardation and subsequent short stature, we used single-strand conformation polymorphism analysis, followed by direct DNA sequencing of any abnormalities found. A second cohort consisted of 50 children with short stature who had elevated circulating IGF-I concentrations. Complete sequencing of the IGF-IR gene was performed with DNA from nine children. We also studied a control group of 43 children with normal birth weights. In the first cohort, we identified one girl who was a compound heterozygote for point mutations in exon 2 of the IGF-IR gene that altered the amino acid sequence to Arg108Gln in one allele and Lys115Asn in the other. Fibroblasts cultured from the patient had decreased IGF-I-receptor function, as compared with that in control fibroblasts. No such mutations were found in the 43 controls. In the second group, we identified one boy with a nonsense mutation (Arg59stop) that reduced the number of IGF-I receptors on fibroblasts. Both children had intrauterine growth retardation and poor postnatal growth. Mutations in the IGF-IR gene that lead to abnormalities in the function or number of IGF-I receptors may also retard intrauterine and subsequent growth in humans.

Endocrine research, Jan 23, 2016

Recent genome-wide association studies (GWASs) have identified many genetic variants associated w... more Recent genome-wide association studies (GWASs) have identified many genetic variants associated with metabolic syndrome (MetS). However, their contribution to MetS in ethnic groups in Tunisia is largely unexplored. In this study, we aim to examine the associations of related loci with a risk of metabolic syndrome in a sample of Tunisians. Overall seven polymorphisms rs7265718, rs10401969, rs762861, rs12310367, rs1562398, rs2059807, rs4420638 located at C20orf152, CILP2, LRPAP1, ZNF664, KLF14, INSR, APOE, respectively, were analyzed in 356 samples from the Tunisian population. Anthropometric and biochemical parameters were assessed. Metabolic syndrome was defined according to the International Diabetes Federation (IDF). We find that LRPAP1-rs762861 C allele increases susceptibility to MetS (OR = 1.39, 95% CI = 0.99-1.95, p = 0.041). Separate analysis in men and women revealed the association of rs762861 among females (OR = 1.6, 95% CI = 1.057-2.41, p = 0.021), but not among males (OR...

Metabolic syndrome and related disorders, Jan 7, 2016

Variants in the fat mass and obesity-associated (FTO) gene are associated with obesity and type 2... more Variants in the fat mass and obesity-associated (FTO) gene are associated with obesity and type 2 diabetes mellitus. This study aims to assess the association of the rs9939609 variant and haplotypes in FTO gene with metabolic syndrome (MetS) components in a Tunisian population sample. A total of 685 Tunisian subjects were genotyped for the rs9939609T>A using TaqMan allelic discrimination assay. Two variants rs1421085T>C and rs8057044A>G already genotyped in a previous study were used to test haplotype association of the FTO gene. Genotype distribution of the variant rs9939609 was different between MetS and controls (P = 0.017). Individuals carrying TA genotypes had a significantly increased risk independently of body mass index or age (P = 0.009). The variant rs9939609 was also associated with impaired fasting glucose (IFG) (P = 0.002). Among the eight haplotypes in the population, the haplotype GCA was significantly associated with a higher risk of developing the MetS, hig...

Journal of Diabetes and its Complications, 2015

Variants in the fat mass and obesity-associated gene (FTO) are associated with obesity and type 2... more Variants in the fat mass and obesity-associated gene (FTO) are associated with obesity and type 2 diabetes. However, the association of FTO variants in the MENA (Middle East and North Africa) region with MetS is largely unknown. In this study, we aimed to investigate the association of FTO gene with MetS and its components in Tunisian population. Two variants in the FTO gene were genotyped: rs1421085 T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C and rs8057044 A&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;G in cases and controls from Tunisian population. Anthropometric and biochemical parameters were assessed. Metabolic syndrome was defined according to the International Diabetes Federation (IDF). The FTO rs1421085 variant conferred an increased risk to MetS (OR=1.61, 95% CI=1.14-2.26, P=0.024) that was abolished when adjusted for fasting plasma glucose (FPG), suggesting that the association may be due to variation in FPG levels. Indeed, this variant was associated to FPG (OR = 1.7, 95% CI=1.23-2.44, P=0.002) independently from BMI or age. The second polymorphism rs8057044 was associated with high blood pressure levels (OR=1.45, 95% CI=1.06-1.99, P=0.019). This is the first study highlighting the association between FTO gene variants and MetS in Tunisian population. These findings provide evidence that FTO gene may play a critical role in leading to MetS in Tunisian population.

Endokrynologia Polska, 2015

Insulin gene VNTR was associated with polycystic ovary syndrome (PCOS) in some studies but not in... more Insulin gene VNTR was associated with polycystic ovary syndrome (PCOS) in some studies but not in others. This couldb be due to the heterogeneity of the definition of PCOS and/or the use of inappropriate gene mapping strategies. In this investigation, the association of VNTR with PCOS was explored in a population of women from Central Europe (377 cases and 105 controls) in whom PCOS was diagnosed according to Rotterdam criteria. Seven SNPs: rs3842756 (G/A), rs3842755 (G/T), rs3842754 (C/T), rs3842753 (A/C), rs3842752 (C/T), rs3842748 (G/C), and rs689 (T/A) were genotyped in a portion of the population (160 cases and 95 controls) by sequencing or by SSO-PCR. Analysis of linkage disequilibrium (LD) pattern allowed selecting three tagSNPs (rs3842754, rs3842748, and rs689), which were genotyped in the rest of the population by KASPar. Six haplotypes were reconstructed, among which three (h1, h2 and h6) were more frequent. Statistical analysis allowed observation of the association of the SNP rs3842748, through its GC genotype, with obesity in PCOS (P = 0.049; OR CI95% 1,59 [1.00-2.51]) and in classical PCOS (YPCOS) (P = 0.010), as well as the correlation of the SNP rs689 and the pair of haplotypes h1/h1 with higher levels of testosteronaemia in the PCOS group, although this was at the limit of significance (P = 0.054) CONCLUSION: These results are in accordance with some studies in literature and highlight the role of insulin gene VNTR in complex metabolic disorders.

Human genetics, 2003

International journal of peptide and protein research, 1993

To develop a common strategy in peptide design for kinase assay, antibody production and affinity... more To develop a common strategy in peptide design for kinase assay, antibody production and affinity purification, we investigated phosphorylation and antigenic properties of peptides immobilized on an aminated polyacrylic resin (Expansin) corresponding to autophosphorylation domains of the insulin receptor tyrosine kinase. Immobilized peptides (1143-1155) and peptide (1314-1330), designated p1151 and p1322, respectively, were good substrates for the insulin receptor with Km of 0.74 and 0.78 mM. By contrast, peptide (952-963), designated p960, was poorly phosphorylated. p1151 showed distinctive behaviour as a substrate, displaying a higher basal phosphorylation, a leftward shift of the insulin dose-response curve (ED50 = 0.7 ng mL-1 insulin compared to 20 ng mL-1 for other substrates) and an inhibition by 90% of receptor autophosphorylation (ID50 = 0.5 mM). Similar substrate behaviour was observed with another tyrosine kinase, the pp60c-src. Antibodies against P1151 and p1322 have comp...

Fertility and sterility, 1986

Blood glucose and pyruvate, plasma insulin, and glucagon levels as well as erythrocyte insulin re... more Blood glucose and pyruvate, plasma insulin, and glucagon levels as well as erythrocyte insulin receptors were measured during an oral glucose tolerance test in 38 normal women before and after 6 months' use of one of three new oral contraceptives containing low doses of 19 nortestosterone-derived progestogens, levonorgestrel, and desogestrel. A slight deterioration of glucose tolerance was observed, with the area under the glucose curve increasing by only 7%, 9%, and 12% after Ovidol (Aaciphar SA, Brussels, Belgium), Marvelon (Organon, SA, Brussels, Belgium), and Trigynon (Schering SA, Brussels, Belgium) administration, respectively. We did not find any argument in favor of the development of a state of insulin resistance in women using these compounds, because erythrocyte receptor binding was not modified and plasma insulin responses to glucose were decreased. The glucose-induced suppression of plasma glucagon levels seemed less effective for treatment with the desogestrel-cont...

Progress in Brain Research, 1979

ABSTRACT

Molecular Biology Reports, 2014

Recent studies have suggested that calpain-10 (CAPN10) gene polymorphisms play a role in the susc... more Recent studies have suggested that calpain-10 (CAPN10) gene polymorphisms play a role in the susceptibility to polycystic ovary syndrome (PCOS). The aim of the present study was to evaluate the possible association between three single nucleotide polymorphisms (SNPs) in CAPN10 gene: UCSNP-43 (rs3792267), UCSNP-19 (rs3842570), and UCSNP-63 (rs5030952) and PCOS in Tunisian cases and control women. Study subjects included 127 women with PCOS (mean age 29.8 ± 4.7 year) and 150 healthy women (mean age 33.5 ± 5.6 year). CAPN10 genotyping was carried-out by direct PCR and PCR-RFLP. Linkage disequilibrium pattern in the genomic region explored was determined by HAPLOVIEW 4.2 while reconstruction of haplotypes was done using PHASE 2.1. The phylogenetic distribution of haplotypes in the population was determined by ARLEQUIN 2.000. Six haplotypes were observed. None of SNPs associated with PCOS or its components while the haplotype H4 associated with the phenotype PCOS-obese (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.025). Moreover the pair of haplotypes H1/H4 strongly associated with high blood-pressure (OR = 14.4, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.012). This work confirms the association of CAPN10 gene with metabolic components in PCOS and highlights the role of haplotypes as strong and efficient genetic markers.

Molecular Basis of Insulin Action, 1985

Biochemical and Biophysical Research Communications, 1985

Biochemical Society transactions, 1993

Diabetes & Metabolism, 2014

Annales d'endocrinologie, Jan 14, 2017

Human Genetics, Apr 10, 2003

Diabetes Metabolism, 2001

Reproductive BioMedicine Online, 2016

Diabetes, 1986

Revue Francaise D Endocrinologie Clinique Nutrition Et Metabolisme, 1994

Endocrine research, Jan 23, 2016

Metabolic syndrome and related disorders, Jan 7, 2016

Journal of Diabetes and its Complications, 2015

Endokrynologia Polska, 2015

Human genetics, 2003

International journal of peptide and protein research, 1993

Fertility and sterility, 1986

Progress in Brain Research, 1979

ABSTRACT

Molecular Biology Reports, 2014

Endocrine Abstracts, 2013

Background: PCOS-associated increased metabolic risk may be selective, owing to its heterogeneous... more Background: PCOS-associated increased metabolic risk may be selective, owing to its heterogeneous nature. Identification of high-risk individuals could enable better studies and prevention of complications.

Aim: To characterize the metabolic risk, as metabolic syndrome (MetS), of specific PCOS subphenotypes.

Subjects and methods: Romanian PCOS (Rotterdam criteria) and 64 controls, 18–35 years. PCOS subphenotypes were defined: i) oligo-amenorrhoea (OA), hyperandrogenism (H), and polycystic ovarian morphology (P), OA–H–P (n=143, 59.58%); ii) OA–H (n=35, 14.83%); iii) H–P (n=17, 7.08%) and iv) OA–P (n=45, 18.75%). MetS was defined by harmonized IDF (2009) criteria. Total testosterone (TT), free-androgen index (FAI), insulin-sensitivity index (QUICKI) and SHBG are expressed as mean±SEM and compared by ANCOVA, adjusting for BMI and age. MetS prevalences were compared by χ2-test.

Results: MetS prevalence was higher in OA–H–P and OA–H (28.24 and 35.48%) than in controls (10.42%) (P<0.01). MetS frequencies (13.33 and 17.07%) of H–P and OA–P were not significantly different than controls or OA–H–P and OA–H.

The OA–H–P and OA–H had higher TT (0.84±0.02 and 0.89±0.07 vs 0.67±0.07 ng/ml, P<0.05) and FAI (9.59±0.98 and 7.78±1.04 vs 2.88±0.42, P<0.01) and were more insulin-resistant (QUICKI=0.321±0.003 and 0.313±0.007 vs 0.352±0.005, P<0.05) than controls.

Insulin-sensitivity did not differ significantly between the H–P and OA–P and controls (0.318±0.013 and 0.321±0.006 vs 0.352±0.005). SHBG was lower in OA–H–P and OA–H (58.15±5.34 and 61.49±10.42 vs 132.71±19.39 nmol/l, P<0.01) than in controls.

Conclusions: The oligo-anovulatory hyperandrogenic PCOS have the highest MetS prevalences, suggesting they represent more severe PCOS. The ovulatory and normoandrogenic PCOS subphenotypes were not different than controls in MetS prevalence and insulin-sensitivity, suggesting less metabolic risk. However, direct comparison did not identify significant differences of the same parameters between these two and the more severe PCOS subphenotypes.

Diabetes & Metabolism, 2008

Le gène FTO (fat mass and obesity associated) a été découvert par criblage systématique du génome... more Le gène FTO (fat mass and obesity associated) a été découvert par criblage systématique du génome comme associé au diabète de type 2 et à l’indice de masse corporelle (IMC). Des associations probantes ont été démontrées dans l’obésité morbide chez l’enfant.Afin de comprendre le rôle du FTO dans la résistance à l’insuline dans le syndrome des ovaires polykystiques (SOPK), nous avons exploré les SNP de ce gène dans une population des femmes (n = 104) avec SOPK issues d’Europe Centrale par rapport aux contrôles (n = 83). Une proportion de 29 % des femmes avec SOPK présente une résistance à l’insuline plus sévère par rapport au SOPK maigre (HOMA 6,0 ± 1,0 vs 3,1 ± 0,3), un Acanthosis Nigricans (syndrome HAIRAN) et obésité (IMC 33,6 ± 0,8 vs 23,5 ± 0,4). Le SNP-081 (HapMap) localisé dans l’intron 1 du gène a été génotypé par SSO-PCR (sequence specific oligonucleotide-PCR) et par séquençage. Ce SNP (C/T) est localisé sur un haplotype unique dans la population européenne.La fréquence allélique du SNP-081 a été plus importante dans le SOPK (q = 0,53 vs 0,49) surtout chez les femmes avec obésité. Un effet plus marquant de la prévalence des formes homozygotes (C/C) a été observé avec un dosage génique respectivement de 18, 28,5 et 35,5 % chez les femmes contrôles, SOPK maigres et HAIRAN, (P < 0,05, Chi2). La régression logistique a montré une association du génotype (C/C) au SOPK (p < 0,03, OR 1,39). En ANOVA, des relations plus puissantes ont été retrouvées entre le génotype C/C et la résistance à l’insuline (p < 0,006). Ce résultat a été confirmé par régression logistique montrant une association avec le phénotype insulino-résistant ou celui de syndrome HAIRAN (p < 0,005, OR 3,15). La relation la plus étonnante a été retrouvée avec l’indice HOMA de résistance à l’insuline chez les femmes maigres (p < 0,003, OR 9,3).Ces résultats montrent pour la première fois l’influence du gène FTO dans le SOPK, en relation avec le degré d’obésité ou directement avec la résistance à l’insuline et par ce biais pourrait constituer un marqueur génétique important ayant un rôle prédictif dans la résistance à l’insuline.

Annales d'Endocrinologie, 2006

Fertility and Sterility, 2010

To assess the role of the insulin receptor gene in polycystic ovary syndrome (PCOS) we performed ... more To assess the role of the insulin receptor gene in polycystic ovary syndrome (PCOS) we performed a case-control study in a female population (n ¼ 226) from Central Europe by examining the genetic associations of single nucleotide polymorphisms (rs8107575, rs2245648, rs2245649, rs2963, rs2245655, and rs2962) and inferred haplotypes around exon 9 of this gene. The ancestral T allele of single nucleotide polymorphism rs2963 or the corresponding haplotype (GGTC-C) showed association with PCOS with odds ratio 2.99, 95% confidence interval 1.4-6.3, independent of obesity but related to the presence of Acanthosis nigricans and insulin resistance, metabolic syndrome, or hyperandrogeny, thus providing a frame for future fine mapping of the susceptibility loci in PCOS. (Fertil Steril Ò 2010;94:2389-92.