Table 6.
SNPs associated with serum total choline-containing compounds (µmol/l)
| Total N = 948 | Allele frequency in BIS | SNPs related to choline demanda | Relative contribution (%) | ||
|---|---|---|---|---|---|
| β | 95%CI | p value | |||
| Methionine cycle in 1C pathway | |||||
| BHMT gene rs3733890 | 0.21 | ||||
| 0 | 8.3% (79) | Reference | |||
| 1 | 40.7% (386) | − 26.52 | − 134.76, 81.73 | 0.631 | |
| 2 | 50.9% (483) | 21.81 | − 84.22, 127.85 | 0.686 | |
| PEMT gene rs4646343b | 0.68 | ||||
| 0 | 19.0% (180) | Reference | |||
| 1 | 50.7% (481) | 80.12 | 4.16, 156.08 | 0.039 | |
| 2 | 30.3% (287) | 108.1 | 25.21, 190.98 | 0.011 | |
| Additive model (0 to > 2)c | 49.07 | 8.88, 89.26 | 0.017 | 0.81 | |
| PEMT gene rs7946 | 0.26 | ||||
| 0 | 7.0% (66) | Reference | |||
| 1 | 35.7% (338) | − 18.86 | − 135.53, 97.81 | 0.751 | |
| 2 | 57.4% (544) | 33.44 | − 79.54, 146.42 | 0.561 | |
| CHDH rs9001 | − 0.02 | ||||
| 0 | 1.1% (10) | Reference | |||
| 1 | 15.7% (149) | − 25.2 | − 306.87, 256.47 | 0.861 | |
| 2 | 83.2% (789) | 0.06 | − 273.97, 274.09 | 1 | |
| CHDH rs12676 | − 0.06 | ||||
| 0 | 51.7% (490) | Reference | |||
| 1 | 39.7% (376) | 3.01 | − 57.47, 63.49 | 0.922 | |
| 2 | 8.6% (82) | − 4.37 | − 110.25, 101.5 | 0.935 | |
| Folate cycle in 1C pathway | |||||
| MTHFR gene rs1801133 | 0.22 | ||||
| 0 | 46.5% (441) | Reference | |||
| 1 | 42.2% (400) | − 15.44 | − 75.8, 44.91 | 0.616 | |
| 2 | 11.3% (107) | − 79.47 | − 175.95, 17.01 | 0.106 | |
| MTR gene rs1805087 | − 0.03 | ||||
| 0 | 65.4% (620) | Reference | |||
| 1 | 30.9% (293) | − 17.47 | − 79.96, 45.02 | 0.583 | |
| 2 | 3.7% (35) | 12.17 | − 139.25, 163.59 | 0.875 | |
| MTHFD1 rs2236225 | − 0.05 | ||||
| 0 | 18.2% (173) | Reference | |||
| 1 | 53.2% (504) | 7.11 | − 70.34, 84.57 | 0.857 | |
| 2 | 28.6% (271) | 14.06 | − 71.51, 99.62 | 0.747 | |
| CDP (cytidine diphosphate-choline) pathway | |||||
| CHKA gene rs10791957 | 0.41 | ||||
| 0 | 31.9% (302) | Reference | |||
| 1 | 49.2% (466) | 67.93 | 3.11, 132.75 | 0.04 | |
| 2 | 19.0% (180) | 50.31 | − 32.18, 132.8 | 0.232 | |
| Additive model (0 to > 2)b | 24.64 | − 15.19, 64.47 | 0.225 | 0.36 | |
| Choline transport | |||||
| SLC44A1 gene rs7873987 | 0.15 | ||||
| 0 | 78.4% (743) | Reference | |||
| 1 | 19.9% (189) | − 43.75 | − 115.94, 28.44 | 0.235 | |
| 2 | 1.7% (16) | − 86.38 | − 303.33, 130.57 | 0.435 | |
| SLC44A1 gene rs3199966 | 0.28 | ||||
| 0 | 82.9% (786) | Reference | |||
| 1 | 16.1% (153) | − 67.2 | − 144.99, 10.6 | 0.09 | |
| 2 | 0.9% (9) | − 81.15 | − 368.76, 206.45 | 0.58 | |
| Microbial metabolism of trimethylamine in the gut | |||||
| FMO3 rs2266782 | 0.06 | ||||
| 0 | 32.7% (310) | Reference | |||
| 1 | 52.4% (497) | 3.24 | − 60.37, 66.85 | 0.92 | |
| 2 | 14.9% (141) | − 40.57 | − 129.18, 48.05 | 0.369 | |
Relevant SNPs were also explored against dietary choline with no significance observed
BIS Barwon Infant Study; 1C one-carbon cycle; Genes: BHMT betaine-homocysteine S-methyltransferase; PEMT phosphatidylethanolamine N-methyltransferase; CHDH choline dehydrogenase; MTHFR methylenetetrahydrofolate reductase; MTR methionine synthase; MTHFD1 methylenetetrahydrofolate dehydrogenase 1; CHKA choline kinase alpha; SLC44A1 solute carrier family 44 member 1; FMO3 flavin monooxygenase isoform
aSerum total choline-containing compounds regression adjusted for gestational age at blood collection and child's sex and time interval between maternal serum collection and storage
Note: SNPs were coded as follows: (i) wild type allele (0) for dietary choline partitioning to CDP pathway (ii) wild type allele (2) for dietary choline partitioning to betaine
Interpretation of PEMT gene:
bβ = 93.52, estimated mean increase in serum choline-containing compounds is 93.52 µmol/l for children with heterozygous allele AC (1) compared to the homozygous reference allele AA (0) genotype
bβ = 111.4, estimated mean increase in serum choline-containing compounds is 111.4 µmol/l for children with homozygous allele CC (2) compared to the homozygous reference allele AA (0) genotype
cβ = 51.2, estimated mean increase in serum choline-containing compounds is 51.2 µmol/l for each C allele the child carries
p < 0.05 in bold