Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen γ′ levels

Blood ◽  
2005 ◽  
Vol 106 (13) ◽  
pp. 4176-4183 ◽  
Author(s):  
Shirley Uitte de Willige ◽  
Marieke C. H. de Visser ◽  
Jeanine J. Houwing-Duistermaat ◽  
Frits R. Rosendaal ◽  
Hans L. Vos ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Case Control Study ◽  
Population Based ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Thrombosis Risk ◽  
Increased Risk ◽  
Risk For Thrombosis ◽  
Control Study

We investigated the association between haplotypes of fibrinogen alpha (FGA), beta (FGB), and gamma (FGG), total fibrinogen levels, fibrinogen γ′ (γA/γ′ plus γ′/γ′) levels, and risk for deep venous thrombosis. In a population-based case-control study, the Leiden Thrombophilia Study, we typed 15 haplotype-tagging single nucleotide polymorphisms (htSNPs) in this gene cluster. None of these haplotypes was associated with total fibrinogen levels. In each gene, one haplotype increased the thrombosis risk approximately 2-fold. After adjustment for linkage disequilibrium between the genes, only FGG-H2 homozygosity remained associated with risk (odds ratio [OR], 2.4; 95% confidence interval [95% CI], 1.5-3.9). FGG-H2 was also associated with reduced fibrinogen γ′ levels and reduced ratios of fibrinogen γ′ to total fibrinogen. Multivariate analysis showed that reduced fibrinogen γ′ levels and elevated total fibrinogen levels were both associated with an increased risk for thrombosis, even after adjustment for FGG-H2. A reduced fibrinogen γ′ to total fibrinogen ratio (less than 0.69) also increased the risk (OR, 2.4; 95% CI, 1.7-3.5). We propose that FGG-H2 influences thrombosis risk through htSNP 10034C/T [rs2066865] by strengthening the consensus of a CstF site and thus favoring the formation of γA chain above that of γ′ chain. Fibrinogen γ′ contains a unique high-affinity, nonsubstrate binding site for thrombin, which seems critical for the expression of the antithrombin activity that develops during fibrin formation (antithrombin 1).

scholarly journals Relationship between the IL23R SNPs and Crohn’s Disease Susceptibility and Phenotype in the Polish and Bosnian Populations: A Case-Control Study

2019 ◽  
Vol 16 (9) ◽  
pp. 1551
Author(s):  
Krzysztof Borecki ◽  
Iwona Zawada ◽  
Nermin Nusret Salkić ◽  
Beata Karakiewicz ◽  
Grażyna Adler
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Case Control Study ◽  
Age Of Onset ◽  
Severe Disease ◽  
Polish Population ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Control Study

It is suggested that IL-23/IL-17 axis and single nucleotide polymorphisms (SNPs) of IL23R may have crucial role in pathogenesis of Crohn’s disease (CD). Thus, we sought to assess the IL23R SNPs contribution to susceptibility and phenotype of CD. We recruited 117 CD subjects and 117 controls from Poland and 30 CD subjects and 30 controls from Bosnia and Herzegovina (B&H). Two common IL23R SNPs: rs1004819, rs7517847 were genotyped using TaqMan SNP assays. In the Polish population it was found that allele rs1004819: A increases the risk of CD, while allele rs7517847: A is protective against disease development. In Poles the co-carriage of two IL23R risk genotypes was associated with increased risk of CD. A significantly increased risk of CD early onset was observed in Poles carrying at least one rs7517847: G allele. It was also found that IL23R SNPs may be associated with structuring/penetrating CD behavior, as alleles rs1004819: A and rs7517847: G were significantly less frequent in patients without complications, from Poland and B&H, respectively. Allele rs1004819: A was also significantly more frequent in Poles with penetrating CD. These results confirm IL23R SNPs contribution to CD susceptibility in the Polish population and suggest their impact on early age of onset and more severe disease course.

scholarly journals Risk of pulmonary embolism and deep venous thrombosis in patients with asthma: a nationwide case−control study from Sweden

2017 ◽  
Vol 49 (2) ◽  
pp. 1601014 ◽  
Author(s):  
Bengt Zöller ◽  
Mirnabi Pirouzifard ◽  
Ashfaque A. Memon ◽  
Jan Sundquist ◽  
Kristina Sundquist
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Case Control Study ◽  
Conditional Logistic Regression ◽  
Case Control ◽  
Increased Risk ◽  
Using Data ◽  
Population Controls ◽  
Control Study

Asthma is associated with an increased risk of pulmonary embolism (PE) but little is known about whether asthma is associated with an increased risk of deep venous thrombosis (DVT). The aim in this study was to determine the risk of the first event of PE, DVT or a combination of PE and DVT in patients with asthma.We conducted this nationwide case–control study using data from Swedish nationwide registries. We included 114 366 Swedish-born patients with a first hospital diagnosis of PE, 76 494 patients with DVT and 6854 patients with both PE and DVT in Sweden between 1981 and 2010. We also included five age-, sex- and education-matched population controls. All previous hospital diagnoses of asthma were identified. Conditional logistic regression was used to compute odds ratios with adjustment for potential confounders.Asthma was associated with an adjusted odds ratio for PE of 1.43 (95% CI 1.37–1.50), for DVT of 1.56 (95% CI 1.47–1.65) and for combined PE and DVT of 1.60 (95% CI 1.32–1.93). Asthma was associated with an increased risk of PE, DVT and combined PE and DVT.Thus, the inflammation conferred by asthma seems to have systemic (and not just local) prothrombotic effects with increased risk of both DVT and PE.

scholarly journals Associations of Genetic Variants of miRNA Coding Regions With Pulmonary Tuberculosis Risk in China

2021 ◽  
Author(s):  
Mingwu Zhang ◽  
Zhengwei Liu ◽  
Yelei Zhu ◽  
SongHua Chen ◽  
Bin Chen ◽  
...  
Keyword(s):  
Conditional Logistic Regression ◽  
Population Based ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Female Population ◽  
Online Tool ◽  
Coding Regions ◽  
Increased Risk ◽  
Control Study ◽  
Tuberculosis Risk

Abstract Background Tuberculosis (TB) is the leading cause of death caused by single pathogenic microorganism of mycobacterium tuberculosis(MTB). The study aims to explore the associations of microRNA (miRNA) single nucleotide polymorphisms (SNPs) with pulmonary TB (PTB) risk. Methods A population-based case-control study was conducted, and 168 newly diagnosed smear-positive PTB cases and 251 non-TB controls were recruited. SNPs located within miR-27a (rs895819), miR-423 (rs6505162), miR-196a-2 (rs11614913), miR-146a (rs2910164), miR-618 (rs2682818) were selected and MassARRAY® MALDI-TOF System was employed for genotyping. SPSS19.0 was adopted for statistical analysis, non-conditional logistic regression was performed. Odds ratios (ORs) and 95%confidence intervals (95%CIs) were computed to estimate the associations. Associations of haplotypes with PTB risk was performed with online tool. Results Rs895819 CT/CC genotype was associated with reduced PTB risk among female population (OR= 0.45, 95%CI: 0.23-0.98), p=0.045. Haplotypes (Combined with rs895819, rs2682818, rs2910164, rs6505162 and rs11614913) TCCCT, TAGCC, CCCCC, CCGCT and TCGAT were associated with reduced PTB risk and the ORs were 0.67 (95%CI: 0.45-0.99), 0.49 (0.25-0.94), 0.34 (95%CI: 0.14-0.81), 0.22 (95%CI: 0.06-0.84) and 0.24 (95%CI: 0.07-0.79)，respectively; while the haplotypes of TAGCT, CCCCT, CACCT and TCCAT were associated with increased PTB risk, and the ORs were 3.63 (95%CI: 1.54-8.55), 2.20 (95%CI: 1.00-4.86), 3.90 (95%CI: 1.47-10.36) and 2.95 (95%CI: 1.09-7.99), respectively. Conclusions Rs895819 CT/CC genotype was associated with reduced female PTB risk and haplotype TCCCT, TAGCC, CCCCC, CCGCT and TCGAT were associated with reduced PTB risk, while TAGCT, CCCCT, CACCT and TCCAT were associated with increased risk.

scholarly journals A Novel Polymorphism (rs35612982) in CDKAL1 Is a Risk Factor of Type 2 Diabetes: A Case-Control Study

2019 ◽  
Vol 44 (6) ◽  
pp. 1313-1326 ◽  
Author(s):  
Yanni Tian ◽  
Jing Xu ◽  
Ting Huang ◽  
Jiaqi Cui ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Case Control Study ◽  
Insulin Level ◽  
Northwest China ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Increased Risk ◽  
The Status ◽  
Control Study

Background: The interaction of environmental factors and genetic factors may contribute to the risk of type 2 diabetes (T2D). We aimed to investigate whether age, gender, body mass index (BMI) and lifestyle factors have an effect on the association between the CDKAL1 polymorphisms and T2D. Methods: Eight single nucleotide polymorphisms in CDKAL1 were genotyped by Agena MassARRAY in 508 T2D patients and 503 controls. The association between the CDKAL1 polymorphisms and T2D was evaluated using logistic regression model by calculating OR and 95% CIs. Results: We found a significant association between CDKAL1 polymorphisms (rs4712523, OR 1.42, p = 9.44 × 10–5; rs4712524, OR 1.38, p = 3.28 × 10–4; rs10946398, OR 1.43, p = 6.21 × 10–5; rs7754840, OR 1.43, p = 6.33 × 10–5; rs35612982, OR 1.34, p = 0.0010; and rs10440833, OR 1.32, p = 0.0018) and T2D risk among the Han population from Northwest China. We also found that genetic variants of CDKAL1 could modify the risk of T2D that might be influenced by age, BMI and the status of smoking and drinking. Besides, rs35612982-CT (p = 0.038) and rs10440833-AT (p = 0.044) genotypes were higher insulin level. Conclusion: CDKAL1 rs35612982 (C/T) polymorphism, as a new polymorphism, was associated with the increased risk of T2D in the Han Chinese population. Moreover, the contribution of CDKAL1 polymorphisms to T2D risk seems to be associated with age, gender, BMI, smoking and drinking.

scholarly journals Ornithine Decarboxylase (ODC1) gene variant (rs2302615) is associated with gastric cancer independently of Helicobacter pylori CagA serostatus

2021 ◽  
Author(s):  
Anna K Miller ◽  
Gloria Tavera ◽  
Ricardo Dominguez ◽  
M Constanza Camargo ◽  
Tim Waterboer ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Ornithine Decarboxylase ◽  
Case Control Study ◽  
Population Based ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Snp Association ◽  
High Incidence ◽  
Control Study

The primary cause of gastric cancer is chronic infection with Helicobacter pylori (H.pylori) , particularly the high-risk genotype cagA, and risk modification by human genetic variants. We studied 94 variants in 54 genes for association with gastric cancer, including rs2302615 in ornithine decarboxylase (ODC1), which may affect response to chemoprevention with the ODC inhibitor, eflornithine (difluoromethylornithine; DFMO). Our population-based, case-control study included 1366 individuals (664 gastric cancer cases and 702 controls) from Western Honduras, a high incidence region of Latin America. CagA seropositivity was strongly associated with cancer (OR = 3.6; 95% CI:2.6, 5.1). The ODC1 variant rs2302615 was associated with gastric cancer (OR = 1.36; p= 0.018) in a model adjusted for age, sex, and CagA serostatus. Two additional single nucleotide polymorphisms (SNPs) in CASP1 (rs530537) and TLR4 (rs1927914) genes were also associated with gastric cancer. The ODC1 SNP association with gastric cancer was stronger in individuals who carried the TT genotype at the associating TLR4 polymorphism, rs1927914 (OR = 1.77; p = 1.85 x 10-3). In conclusion, the ODC1 variant, rs2302615, is associated with gastric cancer and supports chemoprevention trials with DFMO, particularly in individuals homozygous for the risk allele, C, at rs2302615.

scholarly journals FV Leiden Mutation and Deep Venous Thrombosis in Vojvodina: A Case-Control Study

2011 ◽  
Vol 30 (1) ◽  
pp. 51-54
Author(s):  
Iva Salatić ◽  
Katarina Kiralj ◽  
Gorana Mitić ◽  
Igor Veselinović ◽  
Dušan Vapa
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Case Control Study ◽  
Factor V Leiden ◽  
Case Control ◽  
Factor V ◽  
Increased Risk ◽  
Fv Leiden ◽  
Heterozygous Carriers ◽  
Control Study

FV Leiden Mutation and Deep Venous Thrombosis in Vojvodina: A Case-Control StudyBetween September 2007 and February 2010, the occurrence of symptomatic deep venous thrombosis (DVT) was investigated in a cohort of 79 consecutive patients. A case-control study inclu ded 71 healthy controls matched with cases for sex and age. The prevalence of factor V G1691A mutation genotype was analyzed. Eighteen cases (22.79%; 95% confidence interval (CI) 13.53% to 32.03%) and four controls (5.63%; 95% CI 0.27% to 10.99%) were heterozygous carriers of FV Leiden (p= 0.025). The odds ratio for DVT was 4.94 (95% CI 1.58 to 15.42) and the relative risk 4.04 (95% CI 1.44-11.38) compared with FV 1691G carriers. Four cases were homozygous carriers of FV Leiden, giving a prevalence of 5.06% (95% CI 0.23 to 9.89%) and no controls, therefore OR and RR calculation was based on the prevalence of homozygotes in the general Caucasian population. The OR for DVT was 47.28 (95% CI 0.04 - 52167.3) and the RR 45.57 (95% CI 0.04 to 49540.77; p=0.025) compared with FV 1691 G carriers. Our study confirms that factor V Leiden carriers in Vojvodina, as in similar studies previously carried out in other populations, have an increased risk of developing DVT. The evaluated risk of DVT in heterozygous carriers of the mutation is four- to five-fold higher, whereas for homozygous carriers it is 45- to 48-fold higher than in non-carriers. These results confirm that patients with DVT and their relatives should undergo screening for FV Leiden mutation.

scholarly journals Impact of PD-1 gene polymorphism and its interaction with tea drinking on susceptibility to tuberculosis

2021 ◽  
Vol 149 ◽  
Author(s):  
Jing Wang ◽  
Mian Wang ◽  
Zihao Li ◽  
Xinyin Wu ◽  
Xian Zhang ◽  
...  
Keyword(s):  
Case Control Study ◽  
Preventive Measures ◽  
Nucleotide Polymorphisms ◽  
Unconditional Logistic Regression ◽  
Negative Interaction ◽  
Single Nucleotide ◽  
High Risk Populations ◽  
Tea Drinking ◽  
The Impact ◽  
Control Study

Abstract The aim of this study was to explore the impact of polymorphism of PD-1 gene and its interaction with tea drinking on susceptibility to tuberculosis (TB). A total of 503 patients with TB and 494 controls were enrolled in this case–control study. Three single-nucleotide polymorphisms of PD-1 (rs7568402, rs2227982 and rs36084323) were genotyped and unconditional logistic regression analysis was used to identify the association between PD-1 polymorphism and TB, while marginal structural linear odds models were used to estimate the interactions. Genotypes GA (OR 1.434), AA (OR 1.891) and GA + AA (OR 1.493) at rs7568402 were more prevalent in the TB patients than in the controls (P < 0.05). The relative excess risk of interaction (RERI) between rs7568402 of PD-1 genes and tea drinking was −0.3856 (95% confidence interval −0.7920 to −0.0209, P < 0.05), which showed a negative interaction. However, the RERIs between tea drinking and both rs2227982 and rs36084323 of PD-1 genes were not statistically significant. Our data demonstrate that rs7568402 of PD-1 genes was associated with susceptibility to TB, and there was a significant negative interaction between rs7568402 and tea drinking. Therefore, preventive measures through promoting the consumption of tea should be emphasised in the high-risk populations.

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