TABLE 3.
Single nucleotide polymorphisms (SNPs) that influenced breast-milk choline metabolite concentration curves in participants given a placebo or choline supplement1
| Group and gene | SNP | W-W | W-V | V-V | Metabolite | Effect2 | Change in slope3 | Change in least-squares mean (95% CI)4 |
| Placebo | ||||||||
| MTHFR | rs1537516 | GG (34)5 | GA (8) | AA (0) | Free Cho | Interaction | −0.00714 | — |
| MTHFR | rs17367629 | GG (34) | GA (7) | AA (0) | Free Cho | Interaction | −0.00693 | — |
| MTHFR | rs3753582 | AA (34) | AC (8) | CC (0) | Free Cho | Interaction | 0.007137 | — |
| MTHFR | rs3753588 | GG (34) | GA (8) | AA (0) | Free Cho | Interaction | −0.00714 | — |
| MTHFR | rs6687229 | CC (34) | CT (8) | TT (0) | Free Cho | Interaction | −0.00714 | — |
| Supplement | ||||||||
| PEMT | rs711352 | GG (22) | GC (18) | CC (3) | Betaine | Main effect | — | 2.0 (1.5, 2.7) |
| Placebo plus supplement | ||||||||
| PEMT | rs711352 | GG (51) | GC (30) | CC (3) | Betaine | Main effect | — | 1.6 (1.3, 2.0) |
W, wild type; V, variant; Free Cho, unesterified choline. Pregnant women at <18 wk gestation were enrolled and randomly assigned to receive either a choline supplement (750 mg choline/d) or a placebo (corn oil) from 18 wk pregnancy to 45 d postpartum. Participants were genotyped for 370 SNPs by using lymphocyte DNA. Each SNP was individually tested for an interaction with dietary intake and a main effect on breast-milk and plasma choline and choline metabolite concentrations among placebo subjects, supplement subjects, and all participants combined. Each comparison was carried out via linear regression analysis in 3 different ways as follows: W-W compared with W-V compared with V-V, W-W + W-V compared with V-V, or W-W compared with W-V + V-V. Comparisons were only carried out for SNPs that had a sample size ≥5 for all groups compared. The results from all 3 SNP configurations were entered by using the PROC MULTTEST procedure (SAS version 9.2; SAS Institute, Chicago, IL) simultaneously.
SNPs with a significant interaction or main effect (P < 0.05). Note that the only significant interactions or main effects were in breast milk.
Change in slope indicates how much the slope of the line predicting the effect of total choline intake on metabolite changes when going from W-W to W-V or V-V. A minus sign indicates that the slope for W-V or V-V subjects was smaller than for W-W subjects.
Change in least-squares mean indicates how much the least-squares mean metabolite concentration (in μmol/L) changed when going from W-W to W-V or V-V.
Genotype; number of participants with the genotype in parentheses (all such values).