Association between human prothrombin variant (T165M) and kidney stone disease

Autor: Nunghathai Sawasdee, Wattanachai Susaengrat, Nirinya Sudtachat, Choochai Nettuwakul, Oranud Praditsap, Pa-thai Yenchitsomanus, Nanyawan Rungroj, Sombat Borvornpadungkitti, Suchai Sritippayawan, Duangporn Chuawattana, Chagkrapan Predanon, Prapaporn Jungtrakoon
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Male
Models
Molecular
Heredity
Protein Conformation
lcsh:Medicine
Gastroenterology
Gene Frequency
Genotype
Gene Order
Kidney Stones
lcsh:Science
Aged
80 and over
Multidisciplinary
Exons
Middle Aged
Nephrology
Medicine
Female
Prothrombin
Research Article
Adult
medicine.medical_specialty
Urology
Genotypes
Molecular Sequence Data
Single-nucleotide polymorphism
Biology
Polymorphism
Single Nucleotide
Molecular Genetics
Kidney Calculi
Young Adult
Sex Factors
Internal medicine
medicine
Genetics
Humans
Genetic Predisposition to Disease
Genetic Testing
Amino Acid Sequence
Allele
Protein Precursors
Codon
Allele frequency
Genetic Association Studies
Aged
Clinical Genetics
Base Sequence
Haplotype
lcsh:R
Case-control study
Computational Biology
Human Genetics
medicine.disease
Molecular biology
Peptide Fragments
Amino Acid Substitution
Kidney stone disease
Case-Control Studies
Genetic Polymorphism
Kidney stones
lcsh:Q
Sequence Alignment
Population Genetics
Zdroj: PLoS ONE, Vol 7, Iss 9, p e45533 (2012)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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