Association of hypoxia‐inducible factor 1A (HIF1A) gene polymorphisms with systemic sclerosis in a French European Caucasian population

Objective.Patients with systemic sclerosis (SSc) exhibit increased toxicity when exposed to genotoxic agents. In our study, we evaluated DNA damage and polymorphic sites in 2 DNA repair genes (XRCC1Arg399Gln andXRCC4Ile401Thr) in patients with SSc.Methods.A total of 177 patients were studied for DNA repair gene polymorphisms. Fifty-six of them were also evaluated for DNA damage in peripheral blood cells using the comet assay.Results.Compared to controls, the patients as a whole or stratified into major clinical variants (limited or diffuse skin involvement), irrespective of the underlying treatment schedule, exhibited increased DNA damage.XRCC1(rs: 25487) andXRCC4(rs: 28360135) allele and genotype frequencies observed in patients with SSc were not significantly different from those observed in controls; however, theXRCC1Arg399Gln allele was associated with increased DNA damage only in healthy controls and theXRCC4Ile401Thr allele was associated with increased DNA damage in both patients and controls. Further, theXRCC1Arg399Gln allele was associated with the presence of antinuclear antibody and anticentromere antibody. No association was observed between these DNA repair gene polymorphic sites and clinical features of patients with SSc.Conclusion.These results corroborate the presence of genomic instability in SSc peripheral blood cells, as evaluated by increased DNA damage, and show that polymorphic sites of theXRCC1andXRCC4DNA repair genes may differentially influence DNA damage and the development of autoantibodies.

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P2Y12 Polymorphisms and the Risk of Adverse Clinical Events in Patients Treated with Clopidogrel: A Meta-Analysis

Drug Research ◽

10.1055/a-0622-8110 ◽

2018 ◽

Vol 69 (01) ◽

pp. 23-31

Author(s):

Kun Zhao ◽

Ming Yang ◽

Yanxia Lu ◽

Shusen Sun ◽

Wei Li ◽

...

Keyword(s):

Gene Polymorphisms ◽

Genetic Model ◽

Statistical Tests ◽

Meta Analysis ◽

Adverse Outcomes ◽

Caucasian Population ◽

Cochrane Library ◽

Bleeding Events ◽

Clinical Events ◽

Ischemic Events

Abstract Background and study aim Some studies have reported an association between P2Y12 gene polymorphisms and clopidogrel adverse outcomes with inconsistent results. We aimed to explore the relationship between P2Y12 polymorphisms and the risk of adverse clinical events in patients treated with clopidogrel through a meta-analysis. Methods A systematic search of PubMed, Web of Science and the Cochrane Library was conducted. Retrieved articles were comprehensively reviewed and eligible studies were included, and the relevant data was extracted for this meta-analysis. All statistical tests were performed by the Review Manager 5.3 software. Results A total of 14 studies involving 8,698 patients were included. In the Han Chinese population, ischemic events were associated with P2Y12 T744C polymorphism in the CC vs TT+CT genetic model (OR=3.32, 95%CI=1.62-6.82, P=0.001), and the events were associated with P2Y12 C34T polymorphism in the TT+TC vs CC genetic model (OR=1.70, 95%CI=1.22-2.36, P=0.002). However, ischemic events were not related to P2Y12 G52T polymorphism (TT+TG vs GG: OR=1.13, 95%CI=0.76-1.68, P=0.56; TT vs GG+TG: OR=2.02, 95%CI=0.65-6.28, P=0.22). The associations between the P2Y12 polymorphism and ischemic events were not significant in T744C, G52T and C34T genotype for another subgroup of the Caucasian population (P>0.05). Only two studies referring to bleeding events were included in this analysis of C34T polymorphism, and no significant association was found (TT+TC vs CC: OR=1.07, 95%CI=0.37-3.15, P=0.90). Conclusions In the Caucasian population, P2Y12 gene polymorphisms are not associated with clinical events. However, in the Chinese Han population, P2Y12 T744C and C34T polymorphisms are significantly associated with adverse clinical events.

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CDA gene polymorphisms and enzyme activity: genotype–phenotype relationship in an Italian–Caucasian population

Pharmacogenomics ◽

10.2217/pgs.13.56 ◽

2013 ◽

Vol 14 (7) ◽

pp. 769-781 ◽

Cited By ~ 16

Author(s):

Francesco M Carpi ◽

Silvia Vincenzetti ◽

Jessica Ubaldi ◽

Stefania Pucciarelli ◽

Valeria Polzonetti ◽

...

Keyword(s):

Enzyme Activity ◽

Gene Polymorphisms ◽

Caucasian Population

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Clinical significance of hypoxia-inducible factor-1 alpha gene polymorphisms in patients with colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.e14045 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. e14045-e14045

Author(s):

Y. Kim ◽

B. Kang ◽

J. Kim ◽

Y. Chae ◽

S. Sohn ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Significance ◽

Gene Polymorphisms ◽

Hypoxia Inducible Factor ◽

Hypoxia Inducible Factor 1 ◽

Alpha Gene

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Hypoxia-inducible factor-1α gene polymorphisms in early and late onset preeclampsia in Sinhalese women

Placenta ◽

10.1016/j.placenta.2014.04.008 ◽

2014 ◽

Vol 35 (7) ◽

pp. 491-495 ◽

Cited By ~ 8

Author(s):

P.H. Andraweera ◽

G.A. Dekker ◽

S.D. Thompson ◽

V.H.W. Dissanayake ◽

R.W. Jayasekara ◽

...

Keyword(s):

Gene Polymorphisms ◽

Late Onset ◽

Hypoxia Inducible Factor ◽

Hypoxia Inducible Factor 1Α

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Lack of association between the polymorphisms of hypoxia-inducible factor 1A (HIF1A) gene and SLE susceptibility in a Chinese population

Immunogenetics ◽

10.1007/s00251-013-0743-4 ◽

2013 ◽

Vol 66 (1) ◽

pp. 9-13 ◽

Cited By ~ 8

Author(s):

Chen-Chen Feng ◽

Qian-Ling Ye ◽

Yan Zhu ◽

Rui-Xue Leng ◽

Gui-Mei Chen ◽

...

Keyword(s):

Chinese Population ◽

Hypoxia Inducible Factor ◽

Hif1a Gene

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Associations between hypoxia-inducible factor-1α (HIF-1α) gene polymorphisms and risk of developing breast cancer

Neoplasma ◽

10.4149/neo_2009_05_441 ◽

2009 ◽

Vol 56 (5) ◽

pp. 441-447 ◽

Cited By ~ 19

Author(s):

R. NAIDU ◽

Y. HAR ◽

N. TAIB

Keyword(s):

Breast Cancer ◽

Gene Polymorphisms ◽

Hypoxia Inducible Factor ◽

Hypoxia Inducible Factor 1Α

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Association Between Thr21Met and Ser89Asn Polymorphisms of the Urotensin II Gene and Systemic Sclerosis

The Journal of Rheumatology ◽

10.3899/jrheum.110509 ◽

2011 ◽

Vol 39 (1) ◽

pp. 106-111 ◽

Cited By ~ 12

Author(s):

YAVUZ PEHLIVAN ◽

BULENT GOGEBAKAN ◽

SERDAR OZTUZCU ◽

METIN OZGEN ◽

GÖZDE YILDIRIM CETIN ◽

...

Keyword(s):

Systemic Sclerosis ◽

Gene Polymorphisms ◽

Turkish Population ◽

Allele Frequencies ◽

Lung Involvement ◽

Urotensin Ii ◽

Finger Flexion ◽

Fibrotic Disorder ◽

Genotype And Allele Frequencies

Objective.Systemic sclerosis (SSc) is an autoimmune chronic fibrotic disorder. Urotensin II (U-II) is predominantly a vasoactive peptide with fibrotic and prothrombotic features. Like endothelin-1 (ET-1), U-II could play an important role in SSc pathogenesis. We evaluated the possible role of the U-II gene polymorphisms (Thr21Met and Ser89Asn) in the genetic susceptibility to SSc in a Turkish population.Methods.A total of 189 patients with SSc and 205 healthy controls were enrolled in our study. We analyzed the genotype and allele frequencies of the U-II (UTS2) gene polymorphisms Thr21Met and Ser89Asn in patients with SSc and in controls.Results.We found that the Thr21Met polymorphism of the UTS2 gene was markedly associated with the risk of developing SSc (p < 0.0001), but there was no relationship between the Ser89Asn polymorphism and SSc (p > 0.05). Two haplotypes (MS and TS) were markedly associated with SSc (p < 0.05). There were significant associations between the genotype and allele frequencies of UTS2 gene Thr21Met polymorphism and cases with diffuse or limited SSc, systemic or lung involvement, finger flexion deformity, pitting scars at the fingertips, positive anticentromere, or positive antitopoisomerase 1 antibody groups.Conclusion.Our study shows the association between Thr21Met, but not Ser89Asn, in the UTS2 gene and SSc. The results strongly suggest that this single-nucleotide polymorphism may be an important risk factor in the development of SSc, and a powerful indicator of severe skin and lung involvement in patients with SSc.

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