Association between Human Prothrombin Variant (T165M) and Kidney Stone Disease
We previously reported the association between prothrombin (F2), encoding a stone inhibitor protein - urinary prothrombin fragment 1 (UPTF1), and the risk of kidney stone disease in Northeastern Thai patients. To identify specific F2 variation responsible for the kidney stone risk, we conducted sequ...
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th-mahidol.133982018-06-11T11:33:48Z Association between Human Prothrombin Variant (T165M) and Kidney Stone Disease Nanyawan Rungroj Nirinya Sudtachat Choochai Nettuwakul Nunghathai Sawasdee Oranud Praditsap Prapaporn Jungtrakoon Suchai Sritippayawan Duangporn Chuawattana Sombat Borvornpadungkitti Chagkrapan Predanon Wattanachai Susaengrat Pa thai Yenchitsomanus Mahidol University Thailand National Center for Genetic Engineering and Biotechnology Khon Kaen Regional Hospital Agricultural and Biological Sciences Biochemistry, Genetics and Molecular Biology We previously reported the association between prothrombin (F2), encoding a stone inhibitor protein - urinary prothrombin fragment 1 (UPTF1), and the risk of kidney stone disease in Northeastern Thai patients. To identify specific F2 variation responsible for the kidney stone risk, we conducted sequencing analysis of this gene in a group of the patients with kidney stone disease. Five intronic SNPs (rs2070850, rs2070852, rs1799867, rs2282687, and rs3136516) and one exonic non-synonymous single nucleotide polymorphism (nsSNP; rs5896) were found. The five intronic SNPs have no functional change as predicted by computer programs while the nsSNP rs5896 (c.494 C > T) located in exon 6 results in a substitution of threonine (T) by methionine (M) at the position 165 (T165M). The nsSNP rs5896 was subsequently genotyped in 209 patients and 216 control subjects. Genotypic and allelic frequencies of this nsSNP were analyzed for their association with kidney stone disease. The frequency of CC genotype of rs5896 was significantly lower in the patient group (13.4%) than that in the control group (22.2%) (P = 0.017, OR 0.54, 95% CI 0.32-0.90), and the frequency of C allele was significantly lower in the patient group (36.1%) than that in the control group (45.6%) (P = 0.005, OR 0.68, 95% CI 0.51-0.89). The significant differences of genotype and allele frequencies were maintained only in the female group (P = 0.033 and 0.003, respectively). The effect of amino-acid change on UPTF1 structure was also examined by homologous modeling and in silico mutagenesis. T165 is conserved and T165M substitution will affect hydrogen bond formation with E180. In conclusion, our results indicate that prothrombin variant (T165M) is associated with kidney stone risk in the Northeastern Thai female patients. © 2012 Rungroj et al. 2018-06-11T04:29:41Z 2018-06-11T04:29:41Z 2012-09-19 Article PLoS ONE. Vol.7, No.9 (2012) 10.1371/journal.pone.0045533 19326203 2-s2.0-84866565522 https://repository.li.mahidol.ac.th/handle/123456789/13398 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84866565522&origin=inward |
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Agricultural and Biological Sciences Biochemistry, Genetics and Molecular Biology Nanyawan Rungroj Nirinya Sudtachat Choochai Nettuwakul Nunghathai Sawasdee Oranud Praditsap Prapaporn Jungtrakoon Suchai Sritippayawan Duangporn Chuawattana Sombat Borvornpadungkitti Chagkrapan Predanon Wattanachai Susaengrat Pa thai Yenchitsomanus Association between Human Prothrombin Variant (T165M) and Kidney Stone Disease |
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We previously reported the association between prothrombin (F2), encoding a stone inhibitor protein - urinary prothrombin fragment 1 (UPTF1), and the risk of kidney stone disease in Northeastern Thai patients. To identify specific F2 variation responsible for the kidney stone risk, we conducted sequencing analysis of this gene in a group of the patients with kidney stone disease. Five intronic SNPs (rs2070850, rs2070852, rs1799867, rs2282687, and rs3136516) and one exonic non-synonymous single nucleotide polymorphism (nsSNP; rs5896) were found. The five intronic SNPs have no functional change as predicted by computer programs while the nsSNP rs5896 (c.494 C > T) located in exon 6 results in a substitution of threonine (T) by methionine (M) at the position 165 (T165M). The nsSNP rs5896 was subsequently genotyped in 209 patients and 216 control subjects. Genotypic and allelic frequencies of this nsSNP were analyzed for their association with kidney stone disease. The frequency of CC genotype of rs5896 was significantly lower in the patient group (13.4%) than that in the control group (22.2%) (P = 0.017, OR 0.54, 95% CI 0.32-0.90), and the frequency of C allele was significantly lower in the patient group (36.1%) than that in the control group (45.6%) (P = 0.005, OR 0.68, 95% CI 0.51-0.89). The significant differences of genotype and allele frequencies were maintained only in the female group (P = 0.033 and 0.003, respectively). The effect of amino-acid change on UPTF1 structure was also examined by homologous modeling and in silico mutagenesis. T165 is conserved and T165M substitution will affect hydrogen bond formation with E180. In conclusion, our results indicate that prothrombin variant (T165M) is associated with kidney stone risk in the Northeastern Thai female patients. © 2012 Rungroj et al. |
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Mahidol University |
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Mahidol University Nanyawan Rungroj Nirinya Sudtachat Choochai Nettuwakul Nunghathai Sawasdee Oranud Praditsap Prapaporn Jungtrakoon Suchai Sritippayawan Duangporn Chuawattana Sombat Borvornpadungkitti Chagkrapan Predanon Wattanachai Susaengrat Pa thai Yenchitsomanus |
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Article |
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Nanyawan Rungroj Nirinya Sudtachat Choochai Nettuwakul Nunghathai Sawasdee Oranud Praditsap Prapaporn Jungtrakoon Suchai Sritippayawan Duangporn Chuawattana Sombat Borvornpadungkitti Chagkrapan Predanon Wattanachai Susaengrat Pa thai Yenchitsomanus |
author_sort |
Nanyawan Rungroj |
title |
Association between Human Prothrombin Variant (T165M) and Kidney Stone Disease |
title_short |
Association between Human Prothrombin Variant (T165M) and Kidney Stone Disease |
title_full |
Association between Human Prothrombin Variant (T165M) and Kidney Stone Disease |
title_fullStr |
Association between Human Prothrombin Variant (T165M) and Kidney Stone Disease |
title_full_unstemmed |
Association between Human Prothrombin Variant (T165M) and Kidney Stone Disease |
title_sort |
association between human prothrombin variant (t165m) and kidney stone disease |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/13398 |
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1763489961897623552 |