Associations between post translational histone modifications, myelomeningocele risk, environmental arsenic exposure, and folate deficiency among participants in a case control study in Bangladesh

Figures & data

Table 1. Characteristics of study population.

Characteristics	Controls (n = 40)	Cases (n = 45)	P-value
Maternal Characteristics
Age at Delivery (years)	22.3 (4.4)	24.5 (5.4)	0.046
Ultrasound During Pregnancy (%)	87.5	88.9	0.84
Reported Folic Acid Use During Pregnancy (%)	60.0	44.4	0.15
Folate Deficiency (%)^*	32.5	33.3	0.94
Plasma Folate (ng/ml)	3.5 (2.6)	4.2 (4.9)	0.39
Infant Characteristics
Sex, Male (%)	60.0	57.8	0.84
Age (Months)	8.4 (5.2)	6.4 (5.7)	0.10

Data are shown as means (standard deviations) for continuous variables or proportions for categorical variables.

* Defined as maternal plasma folate concentration < 4 ng/ml.

Table 2. Distribution of Maternal Arsenic Exposure Levels and Plasma Histone Levels.

Variable	Mean	Standard Deviation	Minimum	25th Percentile	Median	75th Percentile	Maximum
Maternal Arsenic Exposure
Drinking Water Arsenic (µg/L)	35.7	85.8	< LOD^*	< LOD^*	1.73	36.3	506
Maternal Toenail Arsenic (µg/g)	2.19	3.96	< LOD^**	0.38	0.69	2.29	27.7
Plasma Histones
Total H3 (ng/µL)	160	43.2	108	129	158	177	455
H3K27me3 (ng/µL)	31.8	12.0	10.7	24.1	29.2	37.4	71.7
%H3K27me3^#	20.2	6.55	5.92	15.5	19.8	23.7	44.3

* Average LOD for water arsenic samples was 0.15 μg/L.

** Average LOD for toenail arsenic samples was 0.14 µg/g.

^# Calculated by the percentage of the plasma H3K27me3 level divided by the total histone 3 concentration.

LOD, limit of detection.

Table 3. Associations between Plasma Histone Levels and Case Status of Offspring.

Variables	Models^*	OR (95%CI)^#
Total H3 Concentration	Model 1	1.00 (0.99, 1.01)
	Model 2	0.997 (0.99, 1.01)
	Model 3	0.994 (0.98, 1.01)
	Model 4	0.994 (0.98, 1.01)
%H3K27me3	Model 1	0.91 (0.84, 0.98)
	Model 2	0.91 (0.84, 0.98)
	Model 3	0.89 (0.82, 0.98)
	Model 4	0.89 (0.82, 0.98)

* Model 1 was adjusted for infant sex and infant age. Model 2 was adjusted for infant sex, infant age, and ln (maternal plasma folate concentration). Model 3 was adjusted for infant sex, infant age, ln (maternal plasma folate concentration), and ln (maternal toenail arsenic). Model 4 was adjusted for infant sex, infant age, ln (maternal plasma folate concentration), ln (maternal toenail arsenic), and ln (maternal water arsenic).

^# OR: odd ratio; 95%CI: 95% Confidence Interval

Table 4. Associations between Maternal Arsenic with Plasma Histone Levels Stratified by Maternal Folate Status

	Total H3 Concentration				%H3K27me3
	Plasma Folate ≥ 4 ng/ml		Plasma Folate < 4 ng/ml		Plasma Folate ≥ 4 ng/ml		Plasma Folate < 4 ng/ml
Variables	β (SE)	P-value	β (SE)	P-value	β (SE)	P-value	β (SE)	P-value
Ln (Maternal Toenail Arsenic)	−5.24 (5.84)	0.37	−9.99 (3.91)	0.02	−0.51 (0.71)	0.48	−0.27 (1.26)	0.83
Ln (Maternal Water Arsenic)	−3.36 (2.22)	0.14	−2.09 (2.00)	0.31	−0.004 (0.28)	0.99	−0.29 (0.58)	0.62

All models were adjusted for infant sex, infant age, and case status of offspring.