M Guilloud-Bataille

French Institute of Health and Medical Research, Lutetia Parisorum, Île-de-France, France

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Publications (39)115.85 Total impact

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    ABSTRACT: In the sample of 295 French EGEA families with at least one asthmatic subject, a genome screen was conducted to identify potential linkage regions specific either to allergic rhinitis (AR) or to asthma as well as those shared by the two diseases. Two binary rhinitis phenotypes based on (1) diagnosis (ARbin1) and (2) symptoms (ARbin2) and a categorical ordered trait (ARcat) were considered. Asthma phenotype was based on answers to a standardized questionnaire plus the presence of bronchial hyper-responsiveness. Linkage analyses were conducted using the maximum likelihood binomial (MLB) method. These analyses provided potential evidence for linkage to three regions in the whole sample: 1p31 for the phenotype defined by ARbin2 plus asthma (P=0.00016), 2q32 for ARbin2 (P=0.00016) and 3p24-p14 for ARcat (P=0.001). Two other regions were detected in the subset of 185 families with at most one asthmatic sib: 9p22 and 9q22-q34 for ARbin1 (P=0.001 and 0.0007, respectively). No region showed evidence for linkage to asthma without being also linked to AR. While 1p31 may contain a genetic determinant common to asthma and AR, 2q32, 3p24-p14, 9p22 and 9q22-q34 are more likely to harbor genetic factors specific to AR.
    Genes and Immunity 04/2005; 6(2):95-102. · 3.68 Impact Factor
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    ABSTRACT: Using the sample of 107 families with at least two asthmatic siblings, as part of the EGEA study, we have investigated linkage to asthma (or atopy) and genetic heterogeneity according to the presence/absence of atopy (or asthma) using two approaches: (1) the triangle test statistic (TTS), which considers the identical by descent (IBD) distribution among affected sib-pairs discordant for another associated phenotype (eg asthmatic sib-pairs discordant for atopy) and (2) the predivided sample test (PST), which compares the IBD distribution of marker alleles between affected sib-pairs concordant and discordant for the associated phenotype. Two regions, 8p and 12q, already reported to be linked to both asthma and atopy, were examined here. A total of 20 asthmatic sib-pairs discordant for atopy and 24 atopic pairs discordant for asthma were analyzed by both TTS and PST methods and 83 pairs with atopic asthma by PST. Some evidence for linkage was observed for two markers in the 8p23.3-p23.2 region; D8S504 for asthma with genetic heterogeneity according to the presence/absence of atopy and D8S503 for atopy with genetic heterogeneity according to the presence/absence of asthma. In the 12q14.2-q21.33 region, there was also some evidence of linkage to two markers, D12S83 and D12S95, for atopy and asthma, respectively, with genetic heterogeneity according to the presence/absence of the associated trait. Provided the small distance between the two markers on either 8p (16 cM) or 12q (21 cM), it is unclear whether one or two genetic factors are involved in either region.
    European Journal of HumanGenetics 09/2003; 11(8):590-6. · 4.32 Impact Factor
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    ABSTRACT: It is generally believed that an early age at the onset of disease is associated with a stronger genetic component. Our aim here was to investigate both linkage and genetic heterogeneity of asthma, the latter corresponding to different genotype relative risks of a putative linked gene according to age at onset of asthma. This analysis was conducted in 107 French EGEA families with at least two asthmatic siblings, considering 157 markers that were part of our previous genome screen, using the TTS (the Triangle Test Statistic) which has been developed to detect both linkage and intra-sibpair genetic heterogeneity. This test has been applied to 38 asthmatic sib-pairs discordant for age at the onset of asthma. To confirm the existence of genetic heterogeneity, we also used the predivided sample test (PST) which compares the IBD (identity by descent) distribution of marker alleles between asthmatic sib-pairs concordant (67) and discordant (38) for the age at onset. The cutoff point used for the age at onset was 4 years, the median age at onset in our sample of asthmatic sibs. Linkage and genetic heterogeneity for a region located on chromosome 7q (at 109 cM from pter) were indicated by both tests, TTS (P=0.005, P>0.5 after correction for multiple testing) and PST (P=0.0001, 0.015 after correction). These results suggest a genetic factor on 7q involved in asthma with genotype relative risks differing according to age at onset of disease.
    European Journal of HumanGenetics 11/2001; 9(11):867-72. · 4.32 Impact Factor
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    M Gabolde, D Hubert, M Guilloud-Bataille, C Lenaerts, J Feingold, C Besmond
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    ABSTRACT: Chronic liver disease is a major complication of cystic fibrosis. Its incidence and severity show marked heterogeneity, even among the homogeneous group of homozygous DeltaF508 patients, suggesting that environmental or genetic factors other than the deletion DeltaF508 may influence the development of cystic fibrosis related liver disease. We investigated whether the allelic variants of mannose binding lectin, an important protein of the immune system, could be associated with the presence of cirrhosis in a population of 216 homogeneous homozygous DeltaF508 patients. Analysis of the data shows that the presence of cirrhosis in cystic fibrosis patients is significantly associated with a mutated mannose binding lectin genotype (homozygous or compound heterozygous for mannose binding lectin variants). The modulating role of mannose binding lectin in the occurrence of cirrhosis in cystic fibrosis could be explained by the fact that hepatotoxic damage from viruses or bacteria might be increased by the immunodeficiency associated with mannose binding lectin variants and might facilitate the degradation of liver status. These data highlight the crucial role of mannose binding lectin in the clinical outcome of cystic fibrosis, as it has recently been shown that the mannose binding lectin gene is a modulating gene of the respiratory involvement in cystic fibrosis patients.
    Journal of Medical Genetics 06/2001; 38(5):310-1. · 5.70 Impact Factor
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    ABSTRACT: A genome-wide search was conducted in 107 nuclear families with at least two siblings with asthma, as part of the French EGEA study. A two-stage analysis strategy was applied to the 107 families divided into two independent subsets of 46 and 61 families, where all regions detected in the first set of families were tested for replication in the second set. In addition, all regions reported by published genome scans in different populations were examined in the total sample. A total of 254 markers were typed in the first set of families and 70% of them in the second set. Linkage was investigated by model-free methods for asthma and four asthma-related phenotypes: bronchial responsiveness (BR), skin test response, total immunoglobulin E (IgE) levels, and eosinophil count. The two-stage analysis led to the detection of three regions: 11p13 for IgE, 12q24 for eosinophils, and 17q12-21 for asthma and skin tests. Among the regions reported by published genome screens, seven were found in the 107 French EGEA families: three being already detected by the two-stage analysis, 11p13 (p = 0.005), 12q24 (p = 0.0008), and 17q12-21 (p = 0.001), and four additional ones, 1p31 (p = 0.005) for asthma, 11q13 (p = 0.006) for IgE, 13q31 (p = 0.001) for eosinophils, and 19q13 (p = 0.02) for BR.
    American Journal of Respiratory and Critical Care Medicine 12/2000; 162(5):1812-8. · 11.04 Impact Factor
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    ABSTRACT: A subset of 299 patients with homozygous sickle cell anaemia, enrolled in the cohort of the French Study Group on sickle cell disease (SCD), was investigated in this study. The majority of patients were children (mean age 10.1 +/- 5.8 yr) of first generation immigrants from Western and Central Africa, the others originated from the French West Indies (20.2%). We report the frequency of the main clinical events (mean follow-up 4.2 +/- 2.2 yr). The prevalence of meningitis-septicaemia and osteomyelitis was, respectively, 11.4% and 12% acute chest syndrome was observed in 134 patients (44.8%). Twenty patients (6.7%) developed stroke with peak prevalence at 10-15 yr of age. One hundred and seventy-two patients (58%) suffered from one or more painful sickle cell crises, while the others (42.5%) never suffered from pain. The overall frequency of acute anaemic episodes was 50.5%, (acute aplastic anaemia 46%; acute splenic sequestration 26%). A group of 27 patients were asymptomatic (follow-up > 3 yr). Epistatic mechanisms influencing SCD were studied. Coinherited alpha-thalassemia strongly reduced the risk of stroke (p <0.001) and increased that of painful crises (p < 0.02). There was a low prevalence of Senegal and Bantu (CAR) betas-chromosomes in patients with meningitis (p <0.04) and osteomyelitis (p < 0.03). Prevalence of Senegal betas-chromosomes was lower in the asymptomatic group of 27 patients (p < 0.02). The patients come from a population of unmixed immigrants in whom the beta-globin gene haplotype strongly reflects the geographic origin and identifies subgroups with a homogenous genetic background. Thus the observed effects might result more from differences in as yet unidentified determinants in the genetic background than from the direct linkage with differences in the beta-globin gene locus.
    European Journal Of Haematology 10/2000; 65(3):155-64. · 2.55 Impact Factor
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    ABSTRACT: Besides melanoma susceptibility genes and shared environmental exposures, part of the familial clustering of cutaneous malignant melanoma (CMM) might be due to familial aggregation of melanoma-associated phenotypes. Our goal was to assess the patterns of familial aggregation of three melanoma risk factors: great number of naevi (GNN), light phototype (LP) and high degree of sun exposure (HDSE). Familial aggregation of GNN, LP and HDSE was investigated in 66 French families with at least two CMM cases and was measured by the asssociation of the relatives' traits with the probands' traits, using the generalized estimating equations approach. The probands were the melanoma cases leading to ascertainment of the families, subdivided into cases (with the trait studied) and controls (without the trait). We found significant evidence for familial aggregation of GNN only among sibs (OR = 3.7, 95% CI : 1.4-10.5, P = 0.01), of LP among blood relatives (OR = 3.8, 95% CI : 1.8-8.0, P = 0.004) and of HDSE among blood relatives (OR = 4.5, 95% CI : 2.1-9.9, P < 0.001) and spouses (OR = 44.3, 95% CI : 5.1-382.2, P < 10(-3)). These results suggest that genetic factors might account for the clustering of GNN and LP and shared environment for the aggregation of HDSE. The GNN clustering was lower in families with increasing numbers of CMM (>/=3 cases) or presence of p16 mutations, the opposite being observed for LP and HDSE. Moreover, the familial aggregation of LP was significantly lower in families with highly sun-exposed members. Melanoma might not only result from specific genetic and environmental factors but also from those underlying melanoma-associated traits involving complex gene-gene and gene-environment interactions.
    International Journal of Epidemiology 06/2000; 29(3):408-15. · 6.98 Impact Factor
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    M Gabolde, M Guilloud-Bataille, J Feingold, C Besmond
    BMJ Clinical Research 11/1999; 319(7218):1166-7. · 14.09 Impact Factor
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    ABSTRACT: Mannose-binding protein (MBP) is a serum lectin that participates in the innate immune response. MBP deficiency may constitute a risk factor in the development of infections. Three MBP structural variants have been identified with a dominant effect on MBP serum concentration. Similarly, polymorphisms in the promoter of the corresponding gene (HSMBP1B) have been related to variations of MBP concentration in serum. Children with sickle cell disease (SCD) have an increased susceptibility to infections with encapsulated organisms resulting in meningitis, septicaemia, and osteomyelitis. We have investigated the HSMBP1B genotype in 242 children with SCD living in Paris. Apart from the known variant alleles, we identified three novel ones and report their distribution in our sample population. In addition, we found rather unexpectedly an increased frequency of the variant alleles in patients who had not suffered severe infections.
    European Journal of HumanGenetics 10/1999; 7(6):679-86. · 4.32 Impact Factor
  • J Feingold, M Guilloud-Bataille
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    ABSTRACT: Cystic fibrosis (CF) is an autosomal disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Neonatal meconium ileus (MI) occurs in 10-20 percent of newborns with CF. The purpose of this study was to determine the allelic frequencies of the CF mutation in French patients with and without MI and the incidence of MI in 7 homozygotes or compound heterozygotes for mutation of the CFTR gene. Our study confirms the positive association between delta F508, the most frequent CF mutation, G542X mutation and MI and a negative association with G551D.
    Annales de Génétique 02/1999; 42(3):147-50.
  • J Feingold, M Guilloud-Bataille, D De Crozes
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    ABSTRACT: Delta F508 mutation of the CFTR gene is the most frequent deleterious allele involved in cystic fibrosis (CF). We have studied the distribution of the three genotypes, delta F508/delta F508, delta F508/x, x/x, in the American, Canadian and French data registries concerning CF; "x" represents the non-delta F508 mutations. In the three registries the observed distribution of the three genotypes differs from the expected one, calculated according to the Hardy and Weinberg equilibrium. Three factors could explain this discrepancy: Wahlund's effect, misinterpretation of the molecular diagnosis, or an ascertainment bias in relation with the severity of the disease. This last factor is the most likely.
    Annales de Génétique 02/1998; 41(1):31-3.
  • L Briollais, A Chompret, M Guilloud-Bataille, M F Avril, F Demenais
    Melanoma Research - MELANOMA RES. 01/1997; 7.
  • F Demenais, A Chompret, M Guilloud-Bataille, F Grange, M F Avril
    Melanoma Research - MELANOMA RES. 01/1997; 7.
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    ABSTRACT: Prenatal diagnosis (PND) of sickle cell disease (SCD) has been feasible since about 15 years. The number of PND performed for SCD has constantly increased during these years, but its availability raises difficult ethical questions for parents and counsellors. Concerning at-risk parents, only 50% (data in the literature) to 70% (personal data) ask for PND. Our study shows that mainly cultural reasons, then religious ones, educational level and the number of children in the family weigh on the parents' decision to request this diagnosis. The counsellors' position is difficult since clinical severity of the disease is highly variable, there is no early prognostic factor, and the median life expectancy of patients in industrialized countries exceeds 40 years. We need to define a counselling which would consider the image of the illness in the populations involved, in order to help parents understand the implications of the choice they are asked to make.
    Genetic counseling (Geneva, Switzerland) 02/1996; 7(1):9-15. · 0.32 Impact Factor
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    ABSTRACT: Multiple genetic and epidemiological factors are involved in the etiology of cutaneous malignant melanoma. The phenotype defined by a great number of nevi (GNN) is consistently reported as being a major risk factor for melanoma and is likely to be under genetic control. As part of a large genetic and epidemiologic survey of melanoma in France, our goal was to understand the pattern of inheritance of GNN in 295 nuclear families ascertained through 295 melanoma probands. The GNN phenotype was defined as having 50 or more nevi vs. less than 50 nevi. Four percent of the 295 families included at least 2 GNN cases. We found that sun exposure during holidays and propensity to sunburns were significantly associated with GNN, independent of the occurrence of melanoma. Four segregation analyses of GNN were conducted, using the class D regressive logistic model, which differed according to the sampling procedure chosen (with and without the melanoma probands) and the inclusion or not of the significant risk factors. Three of these analyses led to the detection of a recessive-like major factor, which did not fit a Mendelian pattern of inheritance in two of them. Our results are discussed with respect to the low familial clustering of GNN, the type of analysis conducted, the characteristics of the model used, and the complexity of the mechanisms underlying the GNN phenotype.
    Genetic Epidemiology 02/1996; 13(4):385-402. · 4.02 Impact Factor
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    ABSTRACT: Five percent to 10% of cutaneous malignant melanomas (CMMs) occur in a familial setting. Clinical, epidemiologic, and genetic studies of familial CMM in different regions of the world have led to various results. To assess the characteristics of familial CMM in France, the clinical, histologic, and epidemiologic characteristics of 295 patients with CMM were recorded, and a comprehensive familial investigation was performed for each case. Patients with a family history of CMM were compared with nonfamilial cases. Cutaneous malignant melanoma occurred as a familial cancer in 22 (8%) of 295 patients. Among the multiple variables studied, those significantly associated with the familial occurrence of CMM were red hair, inability to tan, and presence of clinically atypical moles. When these variables were considered together in a multivariate analysis, only the association with red hair (P = .001) and atypical moles (P < .05) remained significant. In addition, the patients with familial melanoma exhibited the following tendencies: a younger age at diagnosis, a higher number of moles, and the development of multiple primary melanomas, but these results did not reach statistical significance. Factors relating to UV light exposure, histologic features of CMM, course of the disease, and occurrence of nonmelanoma cancers showed a similar distribution between familial and nonfamilial cases. A familial investigation should be performed for each patient with CMM in France, particularly when he or she exhibits phenotypic risk factors for CMM such as red hair and atypical moles.
    Archives of Dermatology 10/1995; 131(10):1154-9. · 4.79 Impact Factor
  • G Rault, M Guilloud-Bataille, J Feingold
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    ABSTRACT: A national registry for cystic fibrosis was established in France in 1993. A questionnaire is sent once a year to different health care units. The first questionnaire was analyzed in 1992: 1,893 patients (53% males) were identified. 28% were over 15 years of age, 13% more than 20, and 1% over 35. Usually, diagnosis had been suggested by respiratory signs, followed by digestive tract signs and growth impairment and meconial ileus. 13% were diagnosed in screening programmes. Diagnosis was made before 1 year in 66% of the subjects (mean = 7 months). All the data collected and the functional and bacteriologic data were compared with those observed in the United States and Canada. It should also be noted that 38 patients were grafted during this study year and that it is too early to analyze the general outcome for all subjects. The creation of this registry is an important step towards a better understanding of the epidemiology of cystic fibrosis in the French population.
    Revue de Pneumologie Clinique 02/1995; 51(3):115-21. · 0.20 Impact Factor
  • M de Montalembert, M Guilloud-Bataille, J Feingold, R Girot
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    ABSTRACT: The main clinical and haematological features of sickle cell patients were compared in 618 French, 50 Guianese and 87 Algerian patients. In homozygous sickle cell patients, the proportion of icteric subjects rises with age in all centres; the prevalence of splenomegaly reaches a peak in children from 1 to 5 years and then decreases; jaundice and splenomegaly are more often noted in Algerian and Guianese than French patients. The prevalence of painful crisis is comparable in the 3 centres. In 465 French SS children, having a mean age of 7.3 +/- 5.9 years, the prevalence of a past history of meningitis is 7.3%, of septicaemia 4.1% of osteomyelitis 8.8%. These percentages do not differ significantly between countries. Prevalence of a past history of cerebrovascular accident is 3.2% in French SS patients; 1.2% in SC, 3.8% in S beta thalassaemia. A past history of acute splenic sequestration was noted significantly more often in SS (11.75%) and S beta thalassaemia (14.3%) than SC (3.6%) in French children (p < 0.05). Proportions of subjects transfused at least once do not differ between countries; SS children are more transfused (64%) than SC (15.6%) and S beta thalassaemic (66%) (p < 10-4). Haemoglobin and reticulocyte counts do not differ significantly between countries. In conclusion, no major differences were detected between French, Guianese and Algerian homozygous sickle cell patients: this may be due to the fact that France is in itself a mosaïc of ethnic origins.
    European Journal Of Haematology 09/1993; 51(3):136-40. · 2.55 Impact Factor
  • Melanoma Research 02/1993; 3(1):47. · 2.52 Impact Factor