title: Additive effect of ANRIL and BRAP polymorphisms on ankle-brachial index in a Taiwanese population.
abstract: BACKGROUND
  Genetic variations on chromosome 9p21 have been found to be associated with peripheral artery disease (PAD), but have not been investigated in Asians. The ankle-brachial index (ABI) is a widely-used measurement for PAD. We previously reported the BRAP gene is associated with the ABI, so the aim of the present study was to test whether the ANRIL gene on 9p21 is associated with the ABI and to test an interaction between BRAP and ANRIL in a Chinese population.
  
  
  RESULTS
  A total of 745 subjects with a family history of myocardial infarction or stroke were enrolled. The multiplicative and additive effects of 2 significant single-nucleotide polymorphisms (SNPs) were evaluated by multivariable regression analysis. SNP rs2383207 on ANRIL was most significantly associated with lower ABI. Similar to our previous findings, SNP rs11066001 on BRAP was associated with lower ABI. A dose-response relationship between ABI values and the number of risk alleles from the 2 significant SNPs was observed in both men and women (adjusted P=0.004 for men, 0.008 for women). The combined genetic effect on ABI was stronger in smokers than in non-smokers.
  
  
  CONCLUSIONS
  ANRIL on 9p21 and BRAP were both associated with ABI in a Taiwanese population. An additive effect between variants of these 2 genes was found. The finding of a potential gene-gene interaction and gene-environment interaction is interesting, but needs further investigation.
authors: Department of Medical Research, Kaohsiung Medical University Hospital, Taiwan.
authors: Pei-Chien
authors: PC
authors: Tsai
authors: Yi-Chu
authors: YC
authors: Liao
authors: Tsung-Hsien
authors: TH
authors: Lin
authors: Edward
authors: E
authors: Hsi
authors: Yi-Hsin
authors: YH
authors: Yang
authors: Suh-Hang Hank
authors: SH
authors: Juo
mesh_terms: D000328:Adult; D000368:Aged; D055109:Ankle Brachial Index / Q000706:statistics & numerical data*; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D002318:Cardiovascular Diseases / Q000208:ethnology* / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000208:ethnology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000208:ethnology / Q000235:genetics; D020521:Stroke / Q000208:ethnology / Q000235:genetics; D013624:Taiwan / Q000453:epidemiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C561518:CDKN2B antisense RNA, human; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases