Association of genetic variants with hemorrhagic stroke in Japanese individuals

Abstract

Abstract.Although genetic epidemiological studies have implicated several genetic variants as risk factors for hemorrhagic stroke, the genetic determinants of this condition remain largely unknown. We examined an association of genetic variants with intracerebral or subarachnoid hemorrhage among Japanese individuals. The study population comprised 4,304 unrelated Japanese individuals, including 377 subjects with intracerebral hemorrhage, 205 subjects with subarachnoid hemorrhage, and 3,722 controls. The 150 polymorphisms examined in the present study were selected by genome-wide association studies of ischemic stroke and myocardial infarction with the use of the GeneChip Human Mapping 500K Array Set. The chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that the C→T polymorphism (rs1324694) of ERLIN1, the C→T polymorphism (rs12679196) of TRAPPC9, and the G→T polymorphism (rs16936752) of WNK2 were significantly (P<0.05) associated with the prevalence of intracerebral hemorrhage, and that the A→G polymorphism (rs3111754) of ITM2C and the A→G polymorphism (rs10986769) of MAPKAP1 were significantly associated with the prevalence of subarachnoid hemorrhage. Genotypes for ERLIN1, TRAPPC9, and WNK2 may prove informative for assessment of the genetic risk for intracerebral hemorrhage, and those for ITM2C and MAPKAP1 may be beneficial in assessment of the genetic risk for subarachnoid hemorrhage in Japanese individuals.

Heritability and genome‐wide association study of blood pressure in Chinese adult twins

“…A study (Sung et al, 2015 ) about Framingham Heart Study founded that TRAPPC9 was associated with blood pressure. And TRAPPC9 was proved to be related to stroke in study conducted among Japanese (Yoshida et al, 2010 ). So TRAPPC9 might play an important role in regulating pulse pressure by affecting cardiovascular system and blood pressure, but this possible relationship needs to be proved by further researches.…”

Biochemical Structure and Function of TRAPP Complexes in the Cardiac System

“… 17 Plays a protective role against intracerebral hemorrhage. 16 TRAPPC9 regulates neuronal differentiation, NF-κB signaling, and neurogenesis, and variants are linked to intellectual disability, dysmorphic facial features, brain abnormalities, and speech disorders. 61 TRAPPC11 Associated with TRAPPIII.…”

“… 12 , 13 However, TRAPPC subunit variants and/or changes in expression have also been recently associated with structural cardiac diseases such as small-vessel stroke, cardiomyocyte apoptosis, heart looping/atrium placement, and coronary artery disease, and electrical cardiac dysfunction such as atrial fibrillation and Ca 2+ handling defects. 4 , 14 , 15 , 16 , 17 , 18 , 19 , 20 …”

Intracerebral Hemorrhage Genetics

“…Both Endoplasmic Reticulum Lipid Raft Associated 1 ( ERLIN1 ) and Low-Density Lipoprotein Receptor ( LDLR ), located in 10 and 19 chromosomes, respectively, are important in cholesterol homeostasis. The main variants of those genes (rs1324694 for ERLIN1 and rs688 for LDLR ) are associated with a decreased risk of ICH [ 50 , 51 ]. Moreover, they are associated with a protective effect after the ICH.…”

“…The protein encoded by trafficking protein particle complex 9 (TRAPPC) is involved in the neuronal signaling of transcription factors and its overexpression enhances a cytokine-induced NF- κB signaling pathway [ 65 ]. An intronic polymorphism rs12679196 (C allele) has been proved to significantly elevate the risk of ICH in the Japanese population, while the T allele decreased it [ 50 ].…”