Genome screen in the French EGEA study: detection of linked regions shared or not shared by allergic rhinitis and asthma

Dizier, Marie‐Hélène; Bouzigon, Emmanuelle; Guilloud-Bataille, M; Bétard, Christine; Bousquet, Jean; Charpin, D.; Gormand, F.; Hochez, J; Just, Jocelyne; Lemainque, Arnaud; Moual, Nicole Le; Matran, Régis; Neukirch, Françoise; Oryszczyn, Marie-Pierre; Paty, E.; Pin, Isabelle; Vervloët, D.; Kauffmann, F.; Lathrop, Mark; Demenais, Florence; Annesi‐Maesano, Isabella

doi:10.1038/sj.gene.6364163

Cited by 29 publications

(40 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A total of 119 genes were screened by sequencing all exons, flanking intron sequences, 5Ј and 3Ј untranslated regions, and promoter regions in at least 32 DNA samples. The sample consisted of healthy French Caucasian subjects from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA) (10). The sample size allowed us to detect SNPs with a minor allele frequency (MAF) of at least 5% with a probability of 96%.…”

Section: Methodsmentioning

confidence: 99%

“…Patients in the initial phase of type 1 diabetes, that is, duration of diabetes Ͻ5 years, were not included. Established diabetic nephropathy (case subjects) was defined by persistent albuminuria (Ն300 mg/24 h or Ն200 g/min or Ն200 mg/l) in two out of three consecutive 9 University Hospital of Copenhagen, Rigshospitalet, Department of Medical Endocrinology, Copenhagen, Denmark; the 10 Steno Diabetes Center, Copenhagen, Denmark; the 11 Leibniz Institute for Arteriosclerosis Research, Department of Molecular Genetics of Cardiovascular Disease, University of Muenster, Muenster, Germany; the measurements on sterile urine. Patients with clinical or laboratory suspicion of nondiabetic renal or urinary tract disease were excluded.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

G/T Substitution in Intron 1 of the UNC13B Gene Is Associated With Increased Risk of Nephropathy in Patients With Type 1 Diabetes

Trégouët

Groop

McGinn³

et al. 2008

Diabetes

View full text Add to dashboard Cite

OBJECTIVE— Genetic and environmental factors modulate the susceptibility to diabetic nephropathy, as initiating and/or progression factors. The objective of the European Rational Approach for the Genetics of Diabetic Complications (EURAGEDIC) study is to identify nephropathy susceptibility genes. We report molecular genetic studies for 127 candidate genes for nephropathy. RESEARCH DESIGN AND METHODS— Polymorphisms were identified through sequencing of promoter, exon, and flanking intron gene regions and a database search. A total of 344 nonredundant SNPs and nonsynonymous variants were tested for association with diabetic nephropathy (persistent albuminuria ≥300 mg/24 h) in a large type 1 diabetes case/control (1,176/1,323) study from three European populations. RESULTS— Only one SNP, rs2281999, located in the UNC13B gene, was significantly associated with nephropathy after correction for multiple testing. Analyses of 21 additional markers fully characterizing the haplotypic variability of the UNC13B gene showed consistent association of SNP rs13293564 (G/T) located in intron 1 of the gene with nephropathy in the three populations. The odds ratio (OR) for nephropathy associated with the TT genotype was 1.68 (95% CI 1.29–2.19) ( P = 1.0 × 10 −4 ). This association was replicated in an independent population of 412 case subjects and 614 control subjects (combined OR of 1.63 [95% CI 1.30–2.05], P = 2.3 × 10 −5 ). CONCLUSIONS— We identified a polymorphism in the UNC13B gene associated with nephropathy. UNC13B mediates apopotosis in glomerular cells in the presence of hyperglycemia, an event occurring early in the development of nephropathy. We propose that this polymorphism could be a marker for the initiation of nephropathy. However, further studies are needed to clarify the role of UNC13B in nephropathy.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

G/T Substitution in Intron 1 of the UNC13B Gene Is Associated With Increased Risk of Nephropathy in Patients With Type 1 Diabetes

Trégouët

Groop

McGinn³

et al. 2008

Diabetes

View full text Add to dashboard Cite

show abstract

“…In contrast, only two genome-wide searches were conducted for AR in Danish [8] and Japanese [9] family samples. A recent genome scan carried out in French EGEA families for both asthma and allergic rhinitis (AR) [10] , indicated linkage to AR but not to asthma, on chromosomes 2q32, 3p24-p14, 9p22 and 9q22-q34. In contrast, no region showed evidence for linkage to asthma without being also linked to AR.…”

Section: Asthma Plus Allergic Rhinitis Linked To 1p31mentioning

confidence: 99%

Evidence for a Locus in 1p31 Region Specifically Linked to the Co-Morbidity of Asthma and Allergic Rhinitis in the EGEA Study

et al. 2007

View full text Add to dashboard Cite

Objective: A recent genome scan conducted in French EGEA families led to detect linkage of 1p31 to either asthma or allergic rhinitis (AR) and more significantly to asthma associated with AR. The goal of the present study was to assess formally whether 1p31 is a linkage region shared by two different diseases, asthma and AR, or whether it is specific to the co-morbidity asthma plus AR. Methods: We used two different statistical approaches: the Triangle Test Statistic (TTS) and the Predivided Sample Test (PST), to search for heterogeneity of linkage to 1p31 according to the affection status being defined by either the presence of the two diseases (asthma plus AR) or the presence of only one disease (‘asthma only’ or ‘AR only’ or ‘asthma only or AR only’). Results: While no heterogeneity between the ‘two diseases’ phenotype and the ‘one disease’ phenotype was detected by the TTS, there was significant evidence for heterogeneity (p = 0.00007/0.002 after correction for multiple testing) using the PST. There was no indication of linkage in sib-pairs with ‘one disease’ only, while there was significant evidence for linkage in sib-pairs displaying asthma plus AR (p = 0.0002/0.0016 after correction). Conclusion: The present analysis shows that the co-morbidity, asthma plus AR, represents a phenotypic entity, distinct from asthma only or AR only, controlled by a genetic factor located on 1p31.

show abstract

“…The control sample consisted of French Caucasian subjects from the EGEA study (Epidemiological study on the Genetics and Environment of Asthma). 15 Subjects were both male and female individuals without any disease history. These individuals were not part of the control population included in the case-control study on lung and HÀ ÀN cancers.…”

Section: Snp Discoverymentioning

confidence: 99%

“…We previously re-sequenced 70 genes involved in 3 major repair pathways (BER, NER, MMR) and in the DNA synthesis pathway in a healthy French population 15 to determine common genetic variants and investigate their relationship with lung and HÀ ÀN cancers in a case-control study. 16 In the present study, we extended the SNP discovery in the same population to genes governing DSB repair and DDR pathways.…”

mentioning

confidence: 99%

Variants in DNA double‐strand break repair and DNA damage‐response genes and susceptibility to lung and head and neck cancers

Danoy

Michiels

Dessen

et al. 2008

Intl Journal of Cancer

View full text Add to dashboard Cite

Cigarette smoking is the major risk factor for lung cancer, and together with alcohol for head and neck (HÀ ÀN) cancer. These genotoxics produced DNA damage and particularly double-strand breaks (DSB) that are removed by various repair pathways. To understand the initiation of these cancers, we performed a genotype analysis to correlate some variants in specific genes in a casecontrol study of lung and HÀ ÀN cancers. In a discovery phase, we sequenced DNA samples of 32 healthy Caucasians to describe genetic variants in 30 genes involved in the repair of DSB and in DNA damage response. 625 variants were detected on 29 out of the 30 genes successfully screened by sequencing exons, parts of introns and flanking regions. These included 470 non-exonic variants, from which 33 insertions/deletions, and 155 exonic alterations, corresponding to 59 non synonymous polymorphisms. 223 of these variants were not previously described. In total, 379 variants were successfully genotyped in a case-control study restricted to smokers including 151 lung cases, 251 HÀ ÀN cases, and 172 controls. To account for multiple testing, we associated to each p-value a proportion of false positives (q-value). Haplotypeanalysis suggested potential associations (p < 0.05) between lung cancer and 2 genes (RECQL4 and RAD52), which came with qvalue of 8%, and between HÀ ÀN cancer and 1 gene (DNA-PK) but with q-value of 56%. The 3 genes are key players for regulating the efficiency of DSB repair. Large-scale studies are needed to show if any of these 3 variants are truly associated with an increased risk of cancer.

show abstract

Genome screen in the French EGEA study: detection of linked regions shared or not shared by allergic rhinitis and asthma

Cited by 29 publications

References 38 publications

G/T Substitution in Intron 1 of the UNC13B Gene Is Associated With Increased Risk of Nephropathy in Patients With Type 1 Diabetes

G/T Substitution in Intron 1 of the UNC13B Gene Is Associated With Increased Risk of Nephropathy in Patients With Type 1 Diabetes

Evidence for a Locus in 1p31 Region Specifically Linked to the Co-Morbidity of Asthma and Allergic Rhinitis in the EGEA Study

Variants in DNA double‐strand break repair and DNA damage‐response genes and susceptibility to lung and head and neck cancers

Contact Info

Product

Resources

About