RGD Reference Report - XRCC3 polymorphism is associated with hypertension-induced left ventricular hypertrophy. - Rat Genome Database

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XRCC3 polymorphism is associated with hypertension-induced left ventricular hypertrophy.

Authors: Ariyandy, Andi  Sakai, Chiemi  Ishida, Mari  Mizuta, Ryusei  Miyagawa, Kiyoshi  Tashiro, Satoshi  Kinomura, Aiko  Hiraaki, Koji  Ueda, Keitaro  Yoshizumi, Masao  Ishida, Takafumi 
Citation: Ariyandy A, etal., Hypertens Res. 2018 Jun;41(6):426-434. doi: 10.1038/s41440-018-0038-0. Epub 2018 Apr 6.
RGD ID: 401827272
Pubmed: PMID:29626209   (View Abstract at PubMed)
DOI: DOI:10.1038/s41440-018-0038-0   (Journal Full-text)

Deficiency of X-ray repair cross-complementing protein 3 (XRCC3), a DNA-damage repair molecule, and the 241Met variant of XRCC3 have been reported to increase endoreduplication, which induces polyploidy. The aims of this study were to determine the impact of the XRCC3 polymorphism on the incidence of hypertension-induced left ventricular hypertrophy (LVH) and to investigate the mechanisms underlying any potential relationship. Patients undergoing chronic hemodialysis (n = 77) were genotyped to assess for the XRCC3 Thr241Met polymorphism. The XRCC3 241Thr/Met genotype was more frequent in the LVH (+) group than in the LVH (-) group (42.3 vs. 13.7%, χ2 = 7.85, p = 0.0051). To investigate possible mechanisms underlying these observations, human XRCC3 cDNA of 241Thr or that of 241Met was introduced into cultured CHO cells. The surface area of CHO cells expressing XRCC3 241Met was larger than that expressing 241Thr. Spontaneous DNA double-strand breaks accumulated to a greater degree in NIH3T3 cells expressing 241Met (3T3-241Met) than in those expressing 241Thr (3T3-241Thr). DNA damage caused by radiation induced cell senescence more frequently in 3T3-241Met. The levels of basal and TNF-α-stimulated MCP-1 mRNA and protein secretion were higher in 3T3-241Met. Finally, FACS analysis revealed that the cell percentage in G2/M phase including polyploidy was significantly higher in 3T3-241Met than in 3T3-241Thr. Furthermore, the basal level of MCP-1 mRNA positively correlated with the cell percentage in G2/M phase and polyploidy. These data suggest that the XRCC3 241Met increases the risk of LVH via accumulation of DNA damage, thereby altering cell cycle progression and inducing cell senescence and a proinflammatory phenotype.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
XRCC3HumanLeft Ventricular Hypertrophy susceptibilityIAGP associated with hypertension and DNA:SNP:exon 7: p.T241M (rs861539) (Human)RGD 
Xrcc3RatLeft Ventricular Hypertrophy susceptibilityISOXRCC3 (Homo sapiens)associated with hypertension and DNA:SNP:exon 7: p.T241M (rs861539) (Human)RGD 
Xrcc3MouseLeft Ventricular Hypertrophy susceptibilityISOXRCC3 (Homo sapiens)associated with hypertension and DNA:SNP:exon 7: p.T241M (rs861539) (Human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
XRCC3HumanLeft ventricular hypertrophy susceptibilityIAGP DNA:SNP:exon 7: p.T241M (rs861539) (Human)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Xrcc3  (X-ray repair cross complementing 3)

Genes (Mus musculus)
Xrcc3  (X-ray repair complementing defective repair in Chinese hamster cells 3)

Genes (Homo sapiens)
XRCC3  (X-ray repair cross complementing 3)


Additional Information