Hepatocyte growth factor and retinal arteriolar diameter in Singapore Chinese.
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.
Khor
Chiea C
CC
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
Fan
Qiao
Q
Goh
Liang-Kee
LK
Wong
Tien Y
TY
Li
Yi-Ju
YJ
Cheung
Ning
N
Seielstad
Mark
M
Goh
Denise L M
DL
Young
Terri L
TL
Tai
E-Shyong
ES
Saw
Seang-Mei
SM
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
C066855:HGF protein, human; D017228:Hepatocyte Growth Factor