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Journal of Molecular and Clinical Medicine  2018, Vol. 1 Issue (1): 19-22    DOI: 10.31083/j.jmcm.2018.01.003
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A Common Variant in MTHFD1L is Associated with Increased Risk for Spina Bifida
Paige McKenzie1, Yunping Lei1, Jessica Momb2, Dean Appling2, Richard H. Finnell1, 3, *()
1 Department of Pediatrics, The University of Texas at Austin Dell Medical School, Austin, Texas
2 Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas
3 Current Address: Center for Precision Environmental Health, Departments of Molecular and Cellular Biology and Medicine, Baylor College of Medicine, Houston, Texas
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Abstract  

Genetic polymorphisms within folate pathway genes represent potentially meaningful risk factors for neural tube defects (NTDs). Here we investigated the association of three previously identified polymorphisms in the folate pathway gene MTHFD1L with spina bifida in a U.S. population consisting primarily of Hispanic and non-Hispanic Caucasians. MTHFD1L allele 1 was found to significantly reduce maternal risk of having a baby with spina bifida, while allele 3 significantly increased maternal risk to have a spina bifida baby. This study confirms that rs3832406 is associated with an increased risk of spina bifida.

Key words:  Neural tube defects      Genomic variants      One carbon metabolism      MTHFD1L     
Revised:  13 November 2017      Accepted:  24 November 2017      Published:  20 January 2018     
*Corresponding Author(s):  Richard H. Finnell     E-mail:  finnell@bcm.edu

Cite this article: 

Paige McKenzie, Yunping Lei, Jessica Momb, Dean Appling, Richard H. Finnell. A Common Variant in MTHFD1L is Associated with Increased Risk for Spina Bifida. Journal of Molecular and Clinical Medicine, 2018, 1(1): 19-22.

URL: 

https://jmcm.imrpress.com/EN/10.31083/j.jmcm.2018.01.003     OR     https://jmcm.imrpress.com/EN/Y2018/V1/I1/19

Fig. 1.  Representative distribution of three alleles from GeneMapper. Allele1 size was 155, allele2 size was 158 and allele3 size was 161.

Table 1  Genotype and Allele Frequencies of rs3832406 in NTD and Control Groups
Genotypes Cases Mothers (Case) Mothers (Control) Control
1-1 75 80 74 58
1-2 54 56 40 46
1-3 42 59 34 33
2-2 9 16 12 8
2-3 24 27 10 20
3-3 15 24 8 8
Total 219 262 178 173
Table 2  SHEsis single site test in infants
rs3832406
Allele
155
(freq)
158
(freq)
161
(freq)
164
(freq)
p-value
Case 245
(0.559)
96
(0.219)
96
(0.219)
1
(0.002)
0.767899
Control 196
(0.560)
82
(0.234)
70
(0.200)
2
(0.006)
Table 3  Odds ratio of three alleles in infants
Case/controls Odds ratio CI p-value
Allele 1 0.955163 0.5863033-1.546927 0.853
Allele 2 0.899570 0.6004607-1.348085 0.6076
Allele 3 1.069776 0.7077806-1.620753 0.749
Table 4  SHEsis single site test in mothers
rs3832406
Allele
155
(freq)
158
(freq)
161
(freq)
164
(freq)
p-value
Case 275
(0.525)
115
(0.219)
134
(0.256)
0
(0.000)
0.005188*
Control 223
(0.623)
74
(0.207)
60
(0.168)
1
(0.003)
Table 5  Odds ratio of three alleles in mothers
Case/controls Odds ratio CI p-value
Allele 1 0.5859962 0.3585593-0.9399636 0.029253*
Allele 2 1.146151 0.7721792-1.707832 0.50006
Allele 3 1.76746 1.182570-2.663079 0.00589*
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[1] Robert M, Cabrera, Bogdan J, Wlodarczy k, Richard H. Finnell. Elucidation of Folate-Mediated Cascades in the Developing Neural Tube: Congenital Malformations Induced by Methyltransferase Inhibition[J]. Journal of Molecular and Clinical Medicine, 2018, 1(2): 119-126.
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