Hepatocyte Growth Factor and Retinal Arteriolar Diameter in Singapore Chinese
Received 14 May 2009; received in revised form 25 September 2009; accepted 25 September 2009. published online 01 February 2010. Corrected Proof
Objective
To assess if natural genetic variation in hepatocyte growth factor (HGF) is associated with altered retinal vessel diameter.
Design
Two-stage cohort study.
Participants and Controls
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.
Main Outcome Measures
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 (Pmin = 4.6×10−3) 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-μm increase in retinal arteriolar diameter among children and a 2.5-μm increase in adults (P = 7.0×10−3, analysis of variance; P = 3.0×10−3, 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.
Financial Disclosure(s)
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Available online: •••.
1Section for Genetic Medicine, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore, Republic of Singapore
2Division of Infectious Diseases, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Republic of Singapore
3Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore
4Duke-NUS Graduate Medical School, Singapore, Republic of Singapore
5Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia
6Royal Victorian Eye and Ear Hospital, Melbourne, Australia
7Center for Human Genetics, Duke University, Durham, North Carolina
8Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina
9Population Genetics Group, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Republic of Singapore
10Center for Molecular Epidemiology, National University of Singapore, Singapore, Republic of Singapore
11Department of Paediatrics, National University Hospital and National University of Singapore, Singapore, Republic of Singapore
12Department of Endocrinology, Singapore General Hospital, Singapore, Republic of Singapore
13Department of Epidemiology and Public Health, National University of Singapore, Singapore, Republic of Singapore
Correspondence Chiea C. Khor, MBBS, DPhil, Division of Infectious Diseases, Genome Institute of Singapore, 60 Biopolis Street, no. 02-01, Genome, Singapore 138672, Republic of Singapore
Manuscript no. 2009-647.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
ABSTRACT