Genetic variants in BCMO1 and CD36 are associated with plasma lutein concentrations and macular pigment optical density in humans

Figures & data

Table I. Characteristics and nutrient intake of the 29 male subjects enrolled in the clinical study.^a

Item	Mean ± SD
Age, y	49.7 ± 0.8
Height, cm	174.2 ± 1.2
Weight, kg	71.1 ± 1.3
Plasma analytes
Glucose, mmol/L	4.88 ± 0.09
Triglycerides, mmol/L	0.93 ± 0.07
Total cholesterol, mmol/L	4.91 ± 0.14
HDL cholesterol, mmol/L	1.63 ± 0.08
LDL cholesterol, mmol/L	2.99 ± 0.13
Nutrient intake^a
Total Energy, kJ/d	2406 ± 103
Alcohol, g/d	9.0 ± 2.2
Carbohydrate, g/d	279.1 ± 14.2
Protein, g/d	94.2 ± 4.4
Fat, g/d	98.0 ± 4.9
Lutein+zeaxanthin mg/d	1.3 ± 0.4

^aNutrient intake of the subjects as evaluated, at the beginning of the study (i.e. before the lutein-poor diet), by a 3-day food diary.

Table II. Characteristics of the studied SNPs.

Gene	dbSNP ID	SNP ID	Main allele	Minor allele	MAF (%)^a	Intron (I)/Exon (E)/N (Near the gene)	Possible effect on protein activity/expression
ABCA1	rs2230808	hCV2741104	G	A	24.3	E	NS^b
ABCA1	rs2066718	hCV11720789	G	A	3.5	E	NS
ABCA1	rs2230806	hCV2741051	G	A	28.8	E	NS
ABCA1	rs2230805	hCV2741050	G	A	27.4	E	silent
ABCG5	rs6720173	hCV29001998	G	C	15.2	E	NS
ABCG8	rs4148211	hCV29535502	A	G	35.0	E	NS
ABCG8	rs4148217	hCV375061	C	A	20.2	E	NS
ABCG8	rs6544718	hCV25642779	C	T	20.5	E	NS
BCDO2	rs7123686	hCV22274763	A	C	33.6	I	–
BCMO1	rs12934922	hCV25745282	A	T	45.7	E	NS
BCMO1	rs7501331	hCV^c	T	C	23.6	E	NS
CD36	rs1527483	hCV8315330	C	T	8.0	I	–
CD36	rs1761667	hCV8314499	A	G	45.1	N	?
CD36	rs13230419	hCV1803768	T	C	44.0	N	?
CD36	rs7755	hCV8315318	G	A	43.9	N	?
CD36	rs1984112	hCV12093946	A	G	35.8	N	?
NPC1L1	rs217434	hCV2292875	A	G	18.2	E	silent
NPC1L1	rs217428	hCV29736499	T	G	24.1	I	–
NPC1L1	rs17655652	hCV2625150	T	C	31.8	N	?
SCARB1	rs5888	hCV7497008	C	T	47.2	E	silent
SCARB1	rs4238001	hCV26062113	C	T	13.0	E	NS
SCARB1	intron 5^c	hCV25608758	C	T	10.0	I	–

^aMAF=minor allele frequency as observed in a cohort of 2,994 French subjects which was a subset of the French SU.VI.MAX cohort (42).

^bNS = non-synonymous SNP (missense), indicating a change of amino acid.

^cNot referenced in SNP ID or dbSNP.

? = effect not known, although it may have a possible effect on gene expression. SNPs were genotyped with the SNPlex assay except hCV26062113 and hCV25608758, which were genotyped by TaqMan (see Materials and methods).

Figure 1. A: Plasma lutein concentrations, before and after supplementation, in both the group that took the placebo and the group that took the lutein supplement. White bars: values measured before supplementation. Black bars: values measured after supplementation. Means ± SEM of 15 subjects in placebo group and 14 subjects in lutein group. An asterisk indicates a significant difference (P < 0.05) between values measured before and after the supplementation period in each group (paired t test). B: Individual plasma lutein concentrations, before and after supplementation, in the placebo group. C: Individual plasma lutein concentrations, before and after supplementation, in the lutein-supplemented group.

Figure 2. Base-line plasma lutein concentrations for each BCMO1 rs7501331 genotype. A: uncorrected values. B: Values corrected for plasma total cholesterol. Data are means ± SEM of 28 subjects; n is the number of subjects in each genotype group. An asterisk indicates a significant difference (P < 0.05) between genotype groups (Student's t test).

Figure 3. Base-line plasma lutein concentrations for each CD36 rs13230419 genotype. A: uncorrected values. B: Values corrected for plasma total cholesterol. Data are means ± SEM of 25 subjects; n is the number of subjects in each genotype group. In each figure, different letters indicate significant differences (P < 0.05) between genotype groups (ANOVA).

Table III. BCMO1 haplotypes effects on plasma lutein/zeaxanthin.

Haplotypes		Frequencies^a (%)	Haplotype effect^b
rs12934922	rs7501331
A	C	34.1	0.571
A	T	21.1	0.887
T	C	42.7	–
T	T	2.1	0.368

Plasma lutein/zeaxanthin and BCMO1 SNPs were assessed in 622 French subjects (281 males, 341 females).

^aHaplotype frequencies were estimated using Thesias software (43). The most frequent haplotype (TC) is the reference haplotype.

^bHaplotype effect on plasma lutein/zeaxanthin by comparison to the most frequent haplotype (P value calculated by Student's t test).

Table IV. CD36 haplotypes effects on plasma lutein/zeaxanthin.

rs1984112	rs1761667	rs7755	Haplotype frequencies^a (%)	Haplotype effect^b
A	A	A	10.2	0.992
A	A	G	45.2	–
A	G	A	8.4	0.018
A	G	G	1.9	0.567
G	A	G	0.1	–^c
G	G	A	26.2	0.908
G	G	G	7.9	0.074

Plasma lutein/zeaxanthin and CD36 SNPs were assessed in 622 French subjects (281 males, 341 females).

^aHaplotype frequencies were estimated using Thesias software (43). The most frequent haplotype (AAG) is the reference haplotype.

^bHaplotype effect on plasma lutein/zeaxanthin by comparison to the most frequent haplotype (P value calculated by Student's t test).

^cCould not be calculated because of the too low frequency of this haplotype.

Figure 4. A: MPOD (macular pigment optical density), before and after supplementation, in the group that took the placebo and the group that took the lutein supplement. White bars: values measured before supplementation (before). Black bars: values measured after supplementation (after). Means ± SEM of 15 subjects in placebo group and 14 subjects in lutein group. An asterisk indicates a significant difference (P < 0.05) between values measured before and after the supplementation period in each group (paired t test). B: Individual MPOD before and after supplementation in the lutein-supplemented group (n = 14).

Figure 5. A: MPOD response as a function of plasma lutein response. B: MPOD response as a function of initial MPOD. ‘Response’ indicates the differences between the values measured after the dietary intervention and the values measured before the intervention (n = 29). White dots: subjects in the placebo group. Black dots: subjects in the lutein-supplemented group.

Figure 6. MPOD for each BCMO1 and CD36 genotype. A: BCMO1 rs7501331 genotypes. An asterisk indicates a significant difference (P < 0.05) between genotype groups (Student's t test). B: CD36 rs1761667 genotypes. Different letters indicate significant differences (P < 0.05) between genotype groups (ANOVA); n is the number of subjects in each genotype group.

Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D, . The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004;164: 2335–42.

 PubMed Web of Science ®Google Scholar

Tregouet DA, Escolano S, Tiret L, Mallet A, Golmard JL. A new algorithm for haplotype-based association analysis: the Stochastic-EM algorithm. Ann Hum Genet. 2004;68(Pt 2): 165–77.

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