The Relationship between BCMO1 Gene Variants and Macular Pigment Optical Density in Persons with and without Age-Related Macular Degeneration

Abstract

BackgroundRecent evidence indicates that gene variants related to carotenoid metabolism play a role in the uptake of macular pigments lutein (L) and zeaxanthin (Z). Moreover, these pigments are proposed to reduce the risk for advanced age-related macular degeneration (AMD). This study provides the initial examination of the relationship between the gene variants related to carotenoid metabolism, macular pigment optical density (MPOD) and their combined expression in healthy humans and patients with AMD.Participants and MethodsForty-four participants were enrolled from a general population and a private practice including 20 healthy participants and 24 patients with advanced (neovascular) AMD. Participants were genotyped for the three single nucleotide polymorphisms (SNPs) upstream from BCMO1, rs11645428, rs6420424 and rs6564851 that have been shown to either up or down regulate beta-carotene conversion efficiency in the plasma. MPOD was determined by heterochromatic flicker photometry.ResultsHealthy participants with the rs11645428 GG genotype, rs6420424 AA genotype and rs6564851 GG genotype all had on average significantly lower MPOD compared to those with the other genotypes (p<0.01 for all three comparisons). When combining BCMO1 genotypes reported to have “high” (rs11645428 AA/rs6420424 GG/rs6564851 TT) and “low” (rs11645428 GG/rs6420424 AA/rs6564851 GG) beta-carotene conversion efficiency, we demonstrate clear differences in MPOD values (p<0.01). In patients with AMD there were no significant differences in MPOD for any of the three BCMO1 gene variants.ConclusionIn healthy participants MPOD levels can be related to high and low beta-carotene conversion BCMO1 genotypes. Such relationships were not found in patients with advanced neovascular AMD, indicative of additional processes influencing carotenoid uptake, possibly related to other AMD susceptibility genes. Our findings indicate that specific BCMO1 SNPs should be determined when assessing the effects of carotenoid supplementation on macular pigment and that their expression may be influenced by retinal disease.

The Effect of BCMO1 Gene Variants on Macular Pigment Optical Density in Young Healthy Caucasians

“…While there was no significant effect of single BCMO1 SNPs on MPOD, we investigated triple genotype combinations based on BCMO1 plasma conversion efficiency as it has been investigated in a mixed cohort of participants over the age of 50 years ( 16 ). The triple genotypes were combined as follows; high conversion (SNP1 AA/SNP2 GG/SNP3 TT), low conversion (SNP1 GG/SNP2 AA/SNP3 GG), and medium conversion (remaining SNP1, SNP2, and SNP3 genotypes) frequencies are given in Table 2 .…”

“…A macular pigment densitometer (Macular Metrics II, LLC, Providence, RI, USA) was used to perform heterochromatic flicker photometry (HFP). The protocol followed the standardized protocol for measuring MPOD by HFP ( 25 ) and as previously used in our laboratory ( 16 , 26 ). All participants were considered naive to the HFP procedure and underwent brief training and practice trials before completing the task.…”

“…There is an established association between BCMO1 SNPs and MPOD ( 6 , 15 , 17 ) but it is not well understood how genotypes with high- or low-BCMO1 conversion efficiency affect MPOD, in particular, in persons of different age, gender, and ethnicity. Feigl et al ( 16 ) provided the initial demonstration of the effect of the BCMO1 SNPs rs11645428, rs6564851, and rs6420424 on MPOD variations in a mixed gender group aged over 50 years. They demonstrated that participants with rs11645428 GG, rs6564851 GG, and rs6420424 AA genotypes had lower MPOD compared to the other homozygous and heterozygous BCMO1 genotypes ( 16 ).…”

“…Feigl et al ( 16 ) provided the initial demonstration of the effect of the BCMO1 SNPs rs11645428, rs6564851, and rs6420424 on MPOD variations in a mixed gender group aged over 50 years. They demonstrated that participants with rs11645428 GG, rs6564851 GG, and rs6420424 AA genotypes had lower MPOD compared to the other homozygous and heterozygous BCMO1 genotypes ( 16 ). However, this was not evident in patients with manifest AMD and may also vary with age ( 23 ).…”

Common SNP rs6564851 in the BCO1 Gene Affects the Circulating Levels of β-Carotene and the Daily Intake of Carotenoids in Healthy Japanese Women

“…As described in the Introduction, a genome-wide association study with three different cohorts [13] has revealed that the GG homozygotes showed higher circulating levels of β-carotene than the T allele carriers. Moreover, in vivo studies supportively revealed that the catalytic activity of BCO1 was reduced by 48% in female GG homozygotes and the retinyl palmitate:β-carotene ratio in the TG-rich lipoprotein fraction positively correlated with the rs6564851 T allele, indicating that the GG homozygote is a poor responder to conversion of β-carotene to retinyl esters through retinal and retinol [24,25]. In this context, it is easy to understand that a significant positive association of the circulating β-carotene level with the daily intake of β-carotene equivalent was found in the GG homozygotes, by speculating that in the GG homozygotes the ingested β-carotene may efficiently enter the blood stream without excessive cleavage by BCO1 activity.…”