title: Association of rs2075575 and rs9951307 polymorphisms of AQP-4 gene with leukoaraiosis.
abstract: BACKGROUND
  Leukoaraiosis (LA) is associated with structural and functional vascular changes that correlate with motor and gait disturbances, depressive symptoms, urinary disturbances, and dementia. The blood-brain barrier (BBB) plays a key role in development of lacunar stroke, leukoaraiosis, and other feature of cerebral small-vessel disease, and there are numerous studies examining changes in the BBB with normal aging and in dementia and LA. Aquaporin-4 (AQP-4), the primary water channel protein in the central nervous system, is involved in BBB development, function, and integrity, and its dysfunction induces several neurologic diseases. The aim of our study was to evaluate whether genetic variations in AQP-4 gene are associated with the development of LA.
  
  
  METHODS
  DNA was amplified and the single-nucleotide polymorphisms in AQP-4 gene were investigated by melting curve analysis using real-time polymerase chain reaction.
  
  
  RESULTS
  The frequency of both T allele and CT/TT genotypes of rs2075575 was significantly higher in LA group than in control group (C versus T, P = .0145; CC versus CT/TT, P = .038). However, no significant difference was observed between LA group and control group in rs9951307. Interestingly, the rs9951307 AG + GG genotype may confer a synergistic effect in odds ratio (OR) values when combined with the rs2075575 CT + TT genotypes (OR = 1.65 → 2.51). The C-A haplotype was significantly different between LA group and the control group (P = .005). By stratified analysis, rs2075575 and rs9951307 polymorphisms were statistically significant in the subjects with hypertension and hemoglobin A1c (P < .05), whereas the rs2075575 polymorphism was associated with high serum cholesterol (P < .05) and the rs9951307 polymorphism was associated with low serum homocysteine (P < .05).
  
  
  CONCLUSIONS
  Our results indicate that AQP-4 genetic variations and haplotypes might contribute to the risk factors for LA.
authors.affiliation: Department of Medical Science, Chonbuk National University Graduate School, Jeonju, Republic of Korea; Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea; Department of Biochemistry, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal.
authors.forename: Binod K
authors.initials: BK
authors.lastname: Yadav
authors.affiliation: Department of Neurology, Chonbuk National University Medical School, Jeonju, Republic of Korea; Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Oh
authors.affiliation: Institute for Clinical Research, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea.
authors.forename: Nam-Keun
authors.initials: NK
authors.lastname: Kim
authors.affiliation: Department of Neurology, Chonbuk National University Medical School, Jeonju, Republic of Korea; Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea. Electronic address: sbsneuro@gmail.com.
authors.forename: Byoung-Soo
authors.initials: BS
authors.lastname: Shin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D051401:Aquaporin 4 / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002784:Cholesterol / Q000097:blood; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006442:Glycated Hemoglobin / Q000032:analysis; D006239:Haplotypes; D006801:Humans; D049292:Leukoaraiosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D051401:Aquaporin 4; D015415:Biomarkers; D002784:Cholesterol; D006442:Glycated Hemoglobin; C496030:AQP4 protein, human; C517652:hemoglobin A1c protein, human
keywords: Leukoaraiosis; aquaporin-4; blood–brain barrier; genetic polymorphism