MTHFR A1298C polymorphism: a predictor of reduced risk of preeclampsia in Punjab, Pakistan

Figures & data

Table 1. Comparison of demographic, anthropometric, and clinical parameters among controls and patients.

Parameter	Control group (n = 40)	Preeclampsia group (n = 40)	P- value
Age (years)	29.73 ± 2.76	29.95 ± 5.16	0.809
BMI (kg/m^2)	25.32 ± 2.24	35.00 ± 9.75	<0.001**
GA (weeks)	34.13 ± 3.267	33 ± 3.74	0.175
SBP (mm Hg)	118.5 ± 3.61	154 ± 21.82	<0.001**
DBP (mm Hg)	79.75 ± 6.19	98.73 ± 9.38	<0.001**
PU (mg/dl)	9.78 ± 2.587	212.88 ± 284.476	<0.001**
Parity
nulliparous	13 (32.5)	16 (40)	0.38
primparous	20 (50)	14 (35)
multiparous	7 (17.5)	10 (25)
Gravidity
primigravida	10 (25)	13 (32.5)	0.46
multigravida	30 (75)	27 (67.5)
Family History
No	27 (67.5)	24 (60)	0.48
Yes	13 (32.5)	16 (40)
Edema
No	4 (10%)	2 (5%)	<0.001**
Moderate	32 (80%)	6 15%)
Extreme	4 (10%)	32 (80%)
Headache
No	35 (87.5%)	3 (7.5)	<0.001**
Yes	5 (12.5%)	37 (92.5)
Seizures
No	40 (100%)	36 (90%)	0.116
Yes	0 (0%)	4 (10%)
Epigastric pain
No	40 (100%)	33 (82.5)	0.012*
Yes	0 (0%)	7(17.5)
Abortion
No	35 (87.5)	28 (70)	0.05*
Yes	5 (12.5)	12 (30)

Data is represented as Mean± SD for continuous variables and no. (%) for categorical variables. P- values for continuous variables were calculated using independent t-test or Mann-Whitney U test, and for categorical variables using Chi- square test or Fisher’s exact test depending on the data distribution.

BMI; body mass index, GA; gestational age, SBP; systolic blood pressure, DBP; diastolic blood pressure, PU; proteinuria.

*Significant at the level of 0.05.

**Highly significant at the level of 0.01.

Table 2. Distribution of genotypic and allelic frequencies for MTHFR A1298C polymorphism in the studied population and association for preeclampsia.

Genotypes	Control group N (%)	Preeclampsia group N (%)	χ^2	p^a -value	OR (95% CI)	p^b -value	Adjusted OR (95% CI)^a	p^c - value
A1298C genotype
Codominant model
AA	12 (30)	23 (57.5)	—		1.00^ref		1.00^ref
AC	25 (62.5)	15 (37.5)	5.000	0.02*	0.31 (0.12–0.80)	0.01*	0.19 (0.04–0.87)	0.03*
CC	3 (7.5)	2 (5)	0.213	0.644	0.34 (0.05–2.37)	0.28	0.14 (0.006–3.44)	0.23
Dominant model
AA	12 (30)	23 (57.5)	—		1.00^ref		1.00^ref
AC+CC	28 (70)	17 (42.5)	6.146	0.01*	0.31 (0.12–0.79)	0.01*	0.18 (0.04–0.79)	0.02*
Recessive model
AA+AC	37 (92.5)	38 (95)	—		1.00^ref		1.00^ref
CC	3 (7.5)	2 (5)	0.213	0.644	0.64 (0.10–4.11)	0.64	0.40 (0.02–6.26)	0.52
Overdominant model
AA+CC	16 (40)	24 (60)	—		1.00^ref		1.00^ref
AC	24 (60)	16 (40)	3.200	0.074	0.44 (0.18–1.08)	0.07	0.39 (0.10–1.51)	0.17
Alleles
A allele	49 (61.3)	61(76.3)	—		1.00^ref		1.00^ref
C allele	31 (38.8)	19 (23.8)	4.189	0.04*	0.49 (0.24–0.97)	0.04*	0.42 (0.16–1.142)	0.09
HWE P	0.34

N= number of individuals. % Frequency is shown in parentheses. Differences in the genotype and allele frequencies of MTHFR polymorphism between control and preeclampsia patients were compared using the χ2 test. Odds ratios (OR) with a 95% confidence interval (95% CI) were calculated using logistic regression. Odds ratios are adjusted as OR (95% CI)^a with other co-variates (Age, BMI, gestational age, parity, gravidity, and family history). p^a –value (Chi-square p –value); p^b –value (odds ratio p-value) and p^c -value(Odd ratio p-value after adjustment with other co-variates), HWE; Hardy-Weinberg Equilibrium.

*Significant at the level of 0.05.

Table 3. MTHFR A1298C polymorphism and risk assessment for preeclampsia.

Genotypes	Control group N (%)	Preeclampsia group N (%)	RR (95% CI)	P- value
A1298C genotype
Codominant model
AA	12 (30)	23 (57.5)	1.00^ref
AC	25 (62.5)	15 (37.5)	0.58 (0.12–0.80)	0.01*
CC	3 (7.5)	2 (5)	0.40 (0.07–2.12)	0.28
Dominant model
AA	12 (30)	23 (57.5)	1.00^ref
AC+CC	28 (70)	17 (42.5)	0.60 (0.40–0.91)	0.01*
Recessive model
AA+AC	37 (92.5)	38 (95)	1.00^ref
CC	3 (7.5)	2 (5)	0.66 (0.11–3.77)	0.64
Over dominant model
AA+CC	16 (40)	24 (60)	1.00^ref
AC	24 (60)	16 (40)	0.66 (0.42–1.05)	0.07
Alleles
A allele	49 (61.3)	61 (76.3)	1.00^ref
C allele	31 (38.8)	19 (23.8)	0.61 (0.37–0.99)	0.04*

N= number of individuals. % Frequency is shown in parentheses. Differences in the genotype and allele frequencies of MTHFR polymorphism between control and preeclampsia patients were compared using the χ2 test. Similarly, Risk ratios (RR) with 95% confidence interval (95% CI) and P- values were calculated using the χ2 test.

*Significant at the level of 0.05.

Table 4. Associations between MTHFR A1298C genotype and characteristics among PE patients.

db SNP ID	(1) 1/1	(2) 1/2	(3) 2/2	(1) vs. (2) vs. (3)	(1) vs. (2)	(1) vs. (3)	(2) vs. (3)	(1) + (2) vs. (3)	(1) vs. (2) +(3)	(1) + (3) vs. (2)
(allele1/allele2)	(n)	(n)	(n)	p-value	p- value	p-value	p-value	p-value	p-value	p-value
				OR (95% CI)	OR (95% CI)	OR (95% CI)	OR (95% CI)	OR (95% CI)	OR (95% CI)	OR (95% CI)
rs1801133 (A/C)	23	15	2
Age (years)	30.09 ± 5.67	29.60 ± 4.05	31.00 ± 9.89	0.923	0.959	0.970	0.934	0.772	0.848	0.745
BMI (kg/m^2)	35.66 ± 11.23	34.37 ± 8.01	32.05 ± 0.07	0.845	0.919	0.875	0.949	0.666	0.621	0.756
GA (weeks)	32.57 ± 4.25	33.00 ± 4.40	28.00 ± 2.82	0.310	0.950	0.328	0.279	0.131	0.913	0.576
SBP (mm Hg)	164.7 ± 23.04	152.6 ± 20.86	135 ± 7.07	0.03*	0.145	0.09	0.425	0.08	0.02*	0.142
DBP (mm Hg)	99.9 ± 10.87	97.33 ± 7.03	95.0 ± 7.07	0.606	0.686	0.761	0.943	0.571	0.341	0.475
PU (mg/dl)	363.4 ± 314.2	151.6 ± 112.4	157.5 ± 201.5	0.04*	0.04*	0.521	0.999	0.538	0.01*	0.02*
Parity
Nulliparous	15/23	5/15	1//2	0.06	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref
Primparous	2/23	7/15	0/2		0.01*	0.000*	0*	0*	0.02*	0.01*
					0.09 (0.01–0.61)	—	—	—	0.11 (0.01–0.71)	0.08 (0.01–0.57)
Multiparous	6/23	3/15	1/2		0.64	0.54	0.74	0.58	0.600	0.71
					0.66 (0.12–3.70)	0.40 (0.02–7.48)	0.60 (0.02–13.5)	0.45 (0.02–8.02)	0.124–2.914	0.72 (0.13–3.93)
Gravidity
Primigravida	12/23	4/15	1/2	0.291	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref
Multigravida	11/23	11/15	1/2		0.126	0.953	0.508	0.826	0.04*	0.032*
					3.0 (0.73–12.24)	0.91(0.13–55.1)	2.75 (0.13–55.1)	1.37 (0.08–23.6)	0.23 (0.05–0.9)	0.19 (0.04–0.87)
Family History
No	7/23	10/15	2/2	0.02*	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref
Yes	16/23	5/15	0/2		0.03*	0.999	0.999	0.999	0.01*	0.06
					4.57 (1.13–18.41)	—	—	—	5.48 (1.39–21.59)	3.55 (0.99–13.69)
Edema
No	1/23	1/15	1/2	0.227	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref
Moderate	3/23	2/15	0/2		0.810	0.000*	0*	0*	0.472	0.85
					1.50 (0.05–40.6)	—	—	—	3.00 (0.15–59.8)	0.75 (0.03–14.9)
Extreme	19/23	12/15	1/2		0.753	0.09	0.157	0.08	0.40	0.88
					1.58 (0.09–27.7)	19.0 (0.6–583.3)	12.0 (0.38–374.8)	15.5 (0.68–350.6)	2.92 (0.23–35.6)	0.83 (0.06–10.20)
Headache
No	2/23	1/15	0/2	0.894	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref
Yes	21/23	14/15	2/2		0.821	0.999	0.999	0.999	0.740	0.877
					0.75 (0.06–9.08)	0.00 (0.0–0)	0.00 (0.0–0)	0.00 (0.0–0)	0.65 (0.05–7.89)	0.821 (0.06–9.91)
Seizures
No	19/23	15/23	2/2	0.193	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref
Yes	4/23	0/15	0/2		1.000	0.999	1.000	0.999	0.998	0.998
					—	—	—	—	—	—
Epigastric pain
No	19/23	12/15	2/2	0.783	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref
Yes	4/23	3/15	0/2		0.839	0.999	0.999	0.999	0.983	0.748
					0.84 (0.16–4.43)	—	—	—	0.98 (0.18–5.10)	0.76 (0.14–3.99)
Abortion
No	15/23	12/15	1/2	0.510	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref	1.00^ref
Yes	8/23	3/15	1/2		0.331	0.671	0.373	0.538	0.445	0.291
					0.46 (0.10–2.16)	0.57 (0.02–9.70)	0.25 (0.01–5.26)	0.40 (0.02–7.10)	1.73 (0.42–7.11)	2.25 (0.49–10.14)

Continuous data are expressed as Mean ± Standard deviation and categorical data are expressed as number of genotypes. P- values for continuous variable (Age, BMI, GA, SBP, DBP, and PU) were calculated by Tukey’s HSD (ANOVA) test and P- values for categorical variables (parity, gravidity, family history, edema, headache, seizures, epigastric pain, abortion) were calculated by the Chi- square test. Additionally, P- values for odds ratios and confidence interval were determined by logistic regression.

— Odds ratio cannot be interpreted due to limited sample size.

*significant at the level of 0.05 and **highly significant at the level of 0.01.

Data availability statement

The data that support the findings of this study are available from the corresponding author, (AY), upon reasonable request.