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.

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 (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.