title: Hepatocyte growth factor and retinal arteriolar diameter in Singapore Chinese.
abstract: OBJECTIVE
  To assess if natural genetic variation in hepatocyte growth factor (HGF) is associated with altered retinal vessel diameter.
  
  
  METHODS
  Two-stage cohort study.
  
  
  METHODS
  Discovery set (set 1, n = 682 children) and confirmatory set (set 2, n = 1293 adults).
  
  
  METHODS
  Children in the discovery set were genotyped for a panel of genetic markers within HGF. Markers that were found to be associated significantly with altered retinal vessel diameter then were genotyped in the confirmatory set.
  
  
  METHODS
  Increased or decreased retinal vessel diameter.
  
  
  RESULTS
  In the discovery set (n = 682 Chinese children aged 7 to 12 years), the variant allele of 4 HGF single nucleotide polymorphisms (SNPs) demonstrated association with larger retinal arteriolar diameter. The effect of the variant allele seems to be strongest within a recessive model of inheritance (P(min) = 4.6x10(-3)) for all 4 SNPs. When these 4 SNPs were assessed in a confirmatory study comprising 1293 Chinese adults, successful replication was observed for one of them (HGF +63962; rs5745752); the variant allele was observed to correlate with significantly larger retinal arteriolar diameter, with its effect again strongest within a model of recessive inheritance (P = 0.049). Analyzed as a quantitative trait, recessive carriage at HGF +63962 resulted in on average a 3.5-microm increase in retinal arteriolar diameter among children and a 2.5-microm increase in adults (P = 7.0x10(-3), analysis of variance; P = 3.0x10(-3), Kruskal-Wallis test).
  
  
  CONCLUSIONS
  This study suggests that natural variation within HGF is involved in the control of retinal arteriolar diameter and may be important in the pathogenesis of microvascular disease in individuals of Chinese descent.
authors.affiliation: Section for Genetic Medicine, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore, Republic of Singapore. khorcc@gis.a-star.edu.sg
authors.forename: Chiea C
authors.initials: CC
authors.lastname: Khor
authors.forename: Qiao
authors.initials: Q
authors.lastname: Fan
authors.forename: Liang-Kee
authors.initials: LK
authors.lastname: Goh
authors.forename: Tien Y
authors.initials: TY
authors.lastname: Wong
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Cheung
authors.forename: Mark
authors.initials: M
authors.lastname: Seielstad
authors.forename: Denise L M
authors.initials: DL
authors.lastname: Goh
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
authors.forename: E-Shyong
authors.initials: ES
authors.lastname: Tai
authors.forename: Seang-Mei
authors.initials: SM
authors.lastname: Saw
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001160:Arterioles / Q000473:pathology; D044466:Asian People / Q000208:ethnology*; D002318:Cardiovascular Diseases / Q000235:genetics; D002648:Child; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009216:Myopia / Q000235:genetics; D010781:Photography; D020641:Polymorphism, Single Nucleotide; D012161:Retinal Artery / Q000473:pathology*; D012846:Singapore / Q000453:epidemiology
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor