Table 4. Comparison of genotype distributions between control and infertile men.
| Gene symbol; name | Protein function | SNP (description) | Allelesa | Case genotypesb | Control genotypesb | Adjusted OR for infertility (95% CI)c | |
|---|---|---|---|---|---|---|---|
| Heterozygous | Homozygous for minor alleled | ||||||
| BHMT; betaine-homocysteine methyltransferase | Converts betaine and homocysteine to dimethylglycine and methionine | rs3733890 (R239Q) | G/A | 84/54/11 | 106/65/13 | 0.81 (0.41, 1.61) | 0.63 (0.19, 2.10) |
| TCblR (also known as CD320); transcobalamin receptor | Facilitates the uptake of transcobalamin-bound vitamin B12 into tissues | rs2227288 (G>C: 5′ near gene) | G/C | 120/26/4 | 144/36/3 | 1.34 (0.55, 3.25) | 0.81 (0.09, 7.55) |
| rs173665 (C>T: 3′ near gene) | G/A | 125/24/0 | 141/35/3 | 0.34 (0.15, 0.77) | — | ||
| FOLH1 (also known as GCPII); folate hydrolase (folylpolyglutamate carboxypeptidase) | Hydrolyzes folate polyglutamates | rs61886492 (H475Y) | C/T | 130/17/0 | 168/12/0 | 1.79 (0.62, 5.18) | — |
| MTHFD1; methylenetetrahydrofolate dehydrogenase (NADP+-dependent) 1 | C1-synthase trifunctional enzyme catalyzing the interconversion of 1-carbon derivatives of tetrahydrofolate | rs2236225 (R653Q) | C/T | 53/71/27 | 64/83/36 | 1.24 (0.63, 2.44) | 1.22 (0.50, 2.95) |
| MTHFR; methylenetetrahydrofolate reductase (NAD(P)H) | Converts 5,10-methylenetetra-hydrofolate to 5-methyltetrahydrofolate | rs1801133 (677C>T) | C/T | 73/63/13 | 94/73/15 | 0.93 (0.49, 1.75) | 1.44 (0.45, 4.57) |
| rs1801131 (1298A>C) | A/C | 58/77/11 | 87/62/27 | 1.52 (0.79, 2.94) | 0.24 (0.06, 0.95) | ||
| MTR; methionine synthase (5-methyltetrahydrofolate-homocysteine methyltransferase) | Converts homocysteine and 5-methyltetrahydrofolate to methionine and tetrahydrofolate | rs1805087 (D919G) | A/G | 100/41/6 | 116/57/8 | 1.12 (0.58, 2.19) | 1.52 (0.27, 8.41) |
| MTRR; methionine synthase reductase | Regenerates functional methionine synthase via reductive methylation | rs1801394 (M22I) | G/A | 50/68/32 | 60/88/32 | 0.73 (0.37, 1.47) | 1.43 (0.59, 3.44) |
| rs1532268 (S175 L) | G/A | 59/70/19 | 76/69/36 | 0.83 (0.42, 1.65) | 0.44 (0.18, 1.08) | ||
| PEMT; phosphatidylethanolamine N-methyltransferase | Converts phosphatidyl-ethanolamine to phosphatidylcholine by sequential methylation | rs897453 (V58I) | G/A | 40/74/34 | 52/85/44 | 0.81 (0.38, 1.72) | 0.57 (0.24, 1.36) |
| rs7946 (M175V) | T/C | 77/58/14 | 94/79/8 | 0.87 (0.46, 1.64) | 7.91 (1.60, 39.05) | ||
| rs12325817 (744C>G) | C/G | 42/65/39 | 48/87/43 | 0.79 (0.37, 1.68) | 0.93 (0.40, 2.18) | ||
| SHMT1; serine hydroxymethyl-transferase 1 (soluble) | Converts serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate | rs1979277 (L474F) | G/A | 60/64/27 | 86/81/15 | 0.99 (0.51, 1.92) | 1.93 (0.76, 4.88) |
| RFC1 (also known as SLC19A1); reduced folate carrier | Facilitates the transport of reduced folates into cells | rs1051266 (R27H) | G/A | 48/76/23 | 57/95/27 | 0.79 (0.39, 1.59) | 0.86 (0.33, 2.26) |
| PCFT (also known as SLC46A1);proton-coupled folate transporter | Transport of folate across cell membranes under specific PH conditions | rs9909629 (A>T: 5′ near gene) | A/T | 134/12/0 | 153/26/0 | 0.35 (0.12, 1.03) | — |
| rs11080058 (G>A: 5′ near gene) | G/A | 73/67/8 | 94/72/17 | 1.10 (0.58, 2.09) | 0.39 (0.12, 1.32) | ||
| TCN2; transcobalamin II | Binds cobalamin and mediates its transport into cells | rs9606756 (I23V) | A/G | 113/29/4 | 142/34/4 | 0.92 (0.41, 2.09) | 2.86 (0.30, 26.85) |
| rs1801198 (P259R) | C/G | 45/71/28 | 57/92/29 | 0.76 (0.37, 1.56) | 0.64 (0.25, 1.67) | ||
| rs9621049 (S348F) | C/T | 112/33/3 | 139/35/4 | 1.23 (0.56, 2.69) | 1.84 (0.15, 22.29) | ||
a
Major allele is listed first.
b
Genotype values are numbers of individuals with homozygous major allele/heterozygous/homozygous minor allele.
c
Homozygous for major allele was reference category; logistic regression analysis adjusted for age, education, smoking, use of vitamins, abstinence time, and parents born in Sweden.
d
Homozygote odds ratios were not obtained when there were no cases and/or controls that were homozygous for the minor allele.