scholarly journals The effect of a single nucleotide polymorphism on human α2-antiplasmin activity

Blood ◽  
2007 ◽  
Vol 109 (12) ◽  
pp. 5286-5292 ◽  
Author(s):  
Victoria J. Christiansen ◽  
Kenneth W. Jackson ◽  
Kyung N. Lee ◽  
Patrick A. McKee
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Amino Acid ◽  
Amino Terminus ◽  
Healthy Population ◽  
Plasma Samples ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Genotype Frequencies ◽  
Polymorphic Forms

Abstract The primary inhibitor of plasmin, α2-antiplasmin (α2AP), is secreted by the liver into plasma with Met as the amino-terminus. During circulation, Met-α2AP is cleaved by antiplasmin-cleaving enzyme (APCE), yielding Asn-α2AP, which is crosslinked into fibrin approximately 13 times faster than Met-α2AP. The Met-α2AP gene codes for either Arg or Trp as the sixth amino acid, with both polymorphic forms found in human plasma samples. We determined the Arg6Trp genotype frequency in a healthy population and its effects on Met-α2AP cleavage and fibrinolysis. Genotype frequencies were RR 62.5%, RW 34.0%, and WW 3.5%. The polymorphism related to the percentage of Met-α2AP in plasma was WW (56.4%), RW (40.6%), and RR (23.6%). WW plasma tended to have shorter lysis times than RR and RW plasmas. APCE cleaved purified Met-α2AP(Arg6) approximately 8-fold faster than Met-α2AP(Trp6), which is reflected in Asn-α2AP/Met-α2AP ratios with time in RR, RW, and WW plasmas. Removal of APCE from plasma abrogated cleavage of Met-α2AP. We conclude that the Arg6Trp polymorphism is functionally significant, as it clearly affects conversion of Met-α2AP to Asn-α2AP, and thereby, the rate of α2AP incorporation into fibrin. Therefore, the Arg6Trp polymorphism may play a significant role in governing the long-term deposition/removal of intravascular fibrin.

Characterization of the Human Neutrophil Alloantigen (HNA) 3a.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 24-24 ◽  
Author(s):  
Juergen Bux ◽  
Jan Wesche ◽  
Elke Hammer ◽  
Uwe Voelker ◽  
Angelika Reil ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Amino Acid ◽  
Amino Acid Substitution ◽  
Human Neutrophil ◽  
Plasma Samples ◽  
Nucleotide Polymorphism ◽  
Protein Database ◽  
Single Nucleotide ◽  
Choline Transporter

Abstract Abstract 24 Transfusion-related acute lung injury (TRALI) has been recognized as a frequent cause of transfusion-associated major morbidity and mortality in the Western world. About 80% of reported TRALI cases have been associated with the transfusion of blood products containing leukocyte alloantibodies (Middelburg et al., 2008). Up to 28% of severe and fatal TRALI cases have been reported to be associated with antibodies directed against the human neutrophil alloantigen (HNA)-3a, previously known as 5b (Reil et al., 2008). Since the membrane molecule bearing the HNA-3a/b polymorphism is still unknown, we initiated a study with the objective of elucidating the molecular basis of HNA-3a. For characterization of HNA-3a, we first precipitated HNA-3a from biotinylated HNA-3a expressing neutrophils by the use of HNA-3a antibodies, cell solubilisation with Triton-X100 and Protein G beads coupled with goat anti-human IgG. After electrophoretic separation of the immunoprecipitated proteins by SDS-PAGE and transfer onto membrane, we observed in Western blot analysis a broad band of 80-100 kDa which shifted to 64 kDa after deglycosylation with the N-glycosidase PNGase F. Control plasma samples and/or the use of HNA-3a negative granulocytes did not show these bands. Immunoprecipitates of non-biotinylated granulocytes were purified by μC18 tips and concentrated by vacuum drying. Peptide mixtures were separated and analysed using ultra high performance liquid chromatography and tandem mass spectrometry. Proteins were identified by aligning all obtained spectra with a protein database. Ten peptides were identified which were only present in the HNA-3a precipitates but not in the control precipitates. These peptides were found to be parts of the choline transporter-like protein 2 (CTL2 ) with six peptides matching to the first of the ten extracellular domains. We then assessed a panel of 54 individuals serologically typed for HNA-3a for nonsynonymous mutations in the gene SLC44A2 encoding CTL2 by sequence-specific PCR. The single nucleotide polymorphism 461 G>A resulting in an amino acid substitution from arginine to glutamine at position 154 was fully concordant with the HNA-3a/b phenotypes of these 54 individuals. In addition 461G (154Arg) representing the HNA-3a allele was always found in patients who developed TRALI due to HNA-3a alloantibody transfusion, whereas 461A (154Gln) representing the HNA-3b allele was solely present in all blood donors who formed HNA-3a alloantibodies. In a population study of 3700 individuals using DNA microarrays, 176 (4.8%) were homozygous for A461 (HNA-3b), 1188 (32.1%) were heterozygous (AG461), and 2336 (63.1%) were homozygous for G461 (HNA-3a). Finally, we expressed parts of the first extracellular domain of CTL2 in E. coli which included the amino acid position 154. After culturing, fusion proteins were isolated from the bacteria and transferred on membrane. By immunoblotting, specific signals were only obtained with anti-HNA-3a antibodies containing plasma samples but not with controls. We conclude that the HNA-3a/b polymorphism is caused by a single nucleotide polymorphism at position 461G>A in the gene encoding the choline transporter-like protein 2 resulting in an arginine (R) to glutamine (Q) amino acid substitution at position 154. This finding provides the basis for the development of assays allowing large scale screening of blood donor samples for the presence of HNA-3a antibodies. Such screening will contribute to the reduction of severe TRALI. Disclosures: No relevant conflicts of interest to declare.

BTNL2 gene polymorphism and sarcoid uveitis

2019 ◽  
pp. bjophthalmol-2018-312949 ◽  
Author(s):  
Mayeul Chaperon ◽  
Yves Pacheco ◽  
Delphine Maucort-Boulch ◽  
Jean Iwaz ◽  
Laurent Perard ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Gene Polymorphism ◽  
Nucleotide Polymorphism ◽  
Predisposing Factor ◽  
Single Nucleotide ◽  
Genotype Frequencies ◽  
Subgroup Ii ◽  
Significant Difference ◽  
Caucasian Women ◽  
Patient Subgroups

BackgroundUveitis is a frequent and early feature of sarcoidosis. As BTNL2 (butyrophilin-like 2) gene polymorphism was found linked with the susceptibility to sarcoidosis, we investigated whether a specific genotype of BTNL2 gene G16071A (or rs2076530) single-nucleotide polymorphism (SNP) would be associated with the risk of sarcoid uveitis in all patient subgroups.MethodsThe study compared the genotype frequencies of SNP G16071A of 135 patients with sarcoid uveitis (Sa+Uv+) with those of 196 patients with sarcoidosis without uveitis (Sa+Uv−), 81 patients with uveitis without sarcoidosis (Sa−Uv+), and 271 controls with no sarcoidosis nor uveitis (Sa−Uv−). Three hypothetical subgroups of patients with sarcoid uveitis (Sa+Uv+ cases) were considered: (1) subgroup I: patients aged <45 years of both sexes and all ethnic origins; (2) subgroup II: Caucasian women aged >45 years; and (3) subgroup III: all other patients.ResultsA statistically significant difference in genotype frequencies was found between the groups Sa+Uv− and Sa−Uv− (p=3.2×10−6) and between the groups Sa+Uv+ and Sa+Uv− (p=7.1×10−3). There was no difference between the three subgroups of Sa+Uv+ patients. There was a statistically significant difference in genotype frequencies between Sa+Uv− and Sa+Uv+ subgroup II (p=0.005) but no difference between Sa+Uv− and Sa+Uv+ subgroup I.ConclusionNo association was found between G16071A and the susceptibility to sarcoid uveitis. BTNL2 gene G16071A SNP seems to be a predisposing factor for sarcoidosis except in Caucasian postmenopausal women with sarcoid uveitis in whom the GG genotype prevails. These and future results will help in understanding differences between particular subgroups of patients with sarcoid uveitis.

scholarly journals Polymorphism C/T-13910 of the LCT gene regulatory region and lactase deficiency in Eurasian populations

2007 ◽  
Vol 5 (3) ◽  
pp. 25-34
Author(s):  
Maria V Sokolova ◽  
Eugene V Vasilyev ◽  
Andrey I Kozlov ◽  
Denis V Rebrikov ◽  
Svetlana S Senkeeva ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Regulatory Region ◽  
Recessive Trait ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Genetic Determination ◽  
Asian Populations ◽  
Genotype Frequencies ◽  
European Part Of Russia ◽  
Genetically Determined

Genetically determined deficiency of the lactase enzyme in adults (primary hypolactasia) is a recessive trait. As shown earlier, in some European populations primary hypolactasia is determined by carrying the CC genotype at the single-nucleotide polymorphism (SNP) LCT*С/T-13910. In this work allele and genotype frequencies were estimated for the single-nucleotide polymorphism (SNP) LCT*C/ T-13910 in 7 samples (346 individuals in total), representing Eurasian populations (Saami, Mari, Russians from the Volga-Ural Area, Kazakhs, Uyghurs, Buriats, Arabs). For part of these groups and for some of the earlier studied groups the frequencies of the CC genotype are similar to the epidemiological-clinical data on hypolactasia frequency reported for respective or closely located populations (in Russians, Ukrainians, Byelorussians, Kola Saami, Mari, Komi-Permyaks, Udmurts, Pamir Mountain dwellers, and in Chukchi, Iranians and Arabs). For the Asian populations, the data are contradictory, and evaluation of genetic determination of hypolactasia in these populations requires further studies of larger samples. Considering association of primary hypolactasia with CC genotype in the Russian sample found by us earlier, the obtained results point that the CC genotype at SNP LCT*C/ T-13910 is the main genetic determinant of primary hypolactasia for populations of the European part of Russia.

Dopamine transporter 1 (DAT1) rs40184 single nucleotide polymorphism is not associated with the Malaysian major depressive disorder subjects

2019 ◽  
Vol 2 (4) ◽  
pp. 5-13
Author(s):  
Asraa Faris Aldoghachi ◽  
Pike-See Cheah ◽  
Normala Ibrahim ◽  
Munn Sann Lye ◽  
King-Hwa Ling
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Conditional Logistic Regression ◽  
Nucleotide Polymorphism ◽  
Major Depressive ◽  
Chi Square ◽  
Single Nucleotide ◽  
Malaysian Population ◽  
Genotype Frequencies

Major depressive disorder (MDD) is a serious mental illness with a multifactorial aetiology that was shown to influence behaviour and affect cognition. Previous research has favoured the involvement of dopamine in the aetiology of the disorder, and since one of the critical regulators of the dopamine levels and activity in the brain is DAT1, the present study investigated the association of a single nucleotide polymorphism in the DAT1 gene (rs40184) and MDD in the Malaysian population. A total of 300 cases and 300 matched controls were recruited from four Klang valley hospitals and were screened for DAT1 rs40184 using high resolution melting assays. The allele and genotype frequencies were analysed by using Chi-square. Hardy Weinberg equilibrium for the distribution of alleles and genotypes was tested by using Chi-square. Determination of the association between rs40184 and MDD was achieved by conditional logistic regression using SPSS. In the present study, no significant association was obtained between DAT1 and MDD in the Malaysian population.

scholarly journals The AGT M235T (RS699, 4072T>C) polymorphism is not associated with elite weightlifting performance

2018 ◽  
Vol 23 ◽  
pp. 34
Author(s):  
Sigal Ben-Zaken ◽  
Yoav Meckel ◽  
Dan Nemet ◽  
Michal Pantanowitz ◽  
Alon Eliakim
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Allele Frequency ◽  
Genetic Background ◽  
Elite Athletes ◽  
National Level ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Common Features ◽  
Genotype Frequencies ◽  
The Common

It is now well established that genetic background influences an athlete’s ability to excel in different sport disciplines. Previous studies have demonstrated that among power athletes, single nucleotide polymorphism (SNP) in the AGT genotype (Thr-Thr), was significantly more prevalent among weightlifters compared to sprinters and jumpers indicating that despite the common features of these sport subtypes (short and very intense), they vary in their strength and speed abilities, as well as in their genetic make-up. The aim of the present study was to assess whether the AGT SNP can be used also to distinguish elite from national levels weightlifters. The AGT M235T genotype frequencies were assessed in 47 weightlifters (30 elite, 17 national level) and 86 non-athletes control. The Thr-Thr genotype was significantly higher among weightlifters (29.8%) compared to controls (12.8%) (p=0.048). Thr allele frequency was significantly higher among weightlifters (55.3%) compared to controls (37.8%) (p=0.021). However, there was no difference in the prevalence of the polymorphism between national level and elite athletes. In conclusion, the results suggest that the AGT polymorphism cannot predict elite competitive weightlifting performance.

scholarly journals Single Nucleotide Polymorphism in the Cytolethal Distending Toxin B Gene Confers Heterogeneity in the Cytotoxicity of Actinobacillus actinomycetemcomitans

2006 ◽  
Vol 74 (12) ◽  
pp. 7014-7020 ◽  
Author(s):  
Shuichi Nishikubo ◽  
Masaru Ohara ◽  
Masae Ikura ◽  
Katsuo Katayanagi ◽  
Tamaki Fujiwara ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Amino Acid ◽  
Actinobacillus Actinomycetemcomitans ◽  
Single Amino Acid ◽  
Polymorphism Analysis ◽  
Cytolethal Distending Toxin ◽  
Single Nucleotide Polymorphism Analysis ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Toxin B

ABSTRACT Clinical Actinobacillus actinomycetemcomitans produces cytolethal distending toxin (CDT) with titers ranging from 102 to 108 U/mg. Single nucleotide polymorphism analysis of the cdt gene in clinical isolates identified a variation of a single amino acid at residue 281 of CdtB, which significantly affected CDT toxicity by modulating the chromatin-degrading activity of CdtB.

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