title: The rs4238326 polymorphism in ALDH1A2 gene potentially associated with non-post traumatic knee osteoarthritis susceptibility: a two-stage population-based study.
abstract: A recent genome-wide association study reported significant associations of genetic variants within the ALDH1A2 gene with osteoarthritis (OA) of the hand in European populations. However, these findings have not been well generalized to other joints, or to other populations.
  
  
  
  We performed a two-stage population-based case-control study including 196 non-post traumatic knee OA cases and 442 controls in the first stage and independent 143 non-post traumatic knee OA cases and 238 controls in the second stage in a Chinese population by genotyping eight tagging polymorphisms in ALDH1A2.
  
  
  
  In the first stage, the single nucleotide polymorphism (SNP) rs4238326 was found to be potentially associated with knee OA risk (additive model: odds ratio [OR] = 0.70; 95% confidence interval [95% CI] = 0.49-1.01; P = 0.055), which was further confirmed in the second stage with similar effect (additive model: OR = 0.60; 95% CI = 0.38-0.95; P = 0.029). After combining the two stages, we found that the variant C allele of rs4238326 was probably associated with decreased risk of knee OA (additive model: OR = 0.65; 95% CI = 0.49-0.86; P = 0.003). Furthermore, interaction analyses showed that rs4238326 interacted multiplicatively with age to contribute to knee OA risk (interaction P = 0.041).
  
  
  
  These findings indicate that the SNP rs4238326 in ALDH1A2 gene may potentially modify individual susceptibility to knee OA in the Chinese population. Beyond that, further studies are warranted to validate and extend our findings, and future functional studies are required to clarify the possible mechanisms.
authors.affiliation: Department of Epidemiology, School of Public Health, Nantong University, Nantong, Jiangsu Province, PR China.
authors.forename: M
authors.initials: M
authors.lastname: Chu
authors.affiliation: Department of Epidemiology, School of Public Health, Nantong University, Nantong, Jiangsu Province, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.affiliation: College of Chemistry and Chemical Engineering, Nantong University, Nantong, Jiangsu Province, PR China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Second Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Rong
authors.affiliation: Department of Epidemiology, School of Public Health, Nantong University, Nantong, Jiangsu Province, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Second Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, PR China.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.affiliation: Hongqi Community Health Service Center, Xiangfang District, Harbin, Heilongjiang Province, PR China.
authors.forename: B
authors.initials: B
authors.lastname: Xing
authors.affiliation: Department of Health Education, Public Health College, Harbin Medical University, Harbin, Heilongjiang Province, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Epidemiology, School of Public Health, Nantong University, Nantong, Jiangsu Province, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Department of Epidemiology, School of Public Health, Nantong University, Nantong, Jiangsu Province, PR China. Electronic address: J_meili@126.com.
authors.forename: L
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D000080924:Aldehyde Dehydrogenase 1 Family; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D050697:Retinal Dehydrogenase / Q000235:genetics*
chemical_list: D000080924:Aldehyde Dehydrogenase 1 Family; C545372:ALDH1A2 protein, human; D050697:Retinal Dehydrogenase
keywords: ALDH1A2; Osteoarthritis; Susceptibility; rs4238326