Relationship of MTHFR gene polymorphisms with renal and cardiac disease

doi:10.5527/wjn.v4.i1.127

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World Journal of Nephrology

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World J Nephrol. Feb 6, 2015; 4(1): 127-137
Published online Feb 6, 2015. doi: 10.5527/wjn.v4.i1.127

Table 1 Differences between methylenetetrahydrofolate reductase groups in all patients

	Wild genotype	Heterozygous MTHFR C677T	Heterozygous MTHFR 1298 AC	Compound heterozygous C677T and A1298C	Homozygous MTHFR 1298 CC	Homozygous MTHFR 677TT	P
	(n = 94)	(n = 118)	(n = 76)	(n = 154)	(n = 80)	(n = 104)
Age, yr	53.30 ± 11.89	51.59 ± 17.39	56.74 ± 16.55	57.91 ± 17.04	57.85 ± 14.70	50.12 ± 17.09	< 0.0001
BMI, kg/m²	27.26 ± 5.04	27.28 ± 5.95	28.04 ± 5.84	27.80 ± 6.13	27.01 ± 3.92	28.72 ± 6.61	0.316
GFR	48.84 ± 32.90	66.05 ± 36.70	64.16 ± 36.32	63.31 ± 38.35	61.57 ± 34.91	68.85 ± 27.33	0.002
Triglycerides, mg/dL	109.96 ± 75.73	113.21 ± 57.91	107.63 ± 42.67	128.72 ± 85.29	95.46 ± 37.07	103.94 ± 48.93	0.003
Total cholesterol, mg/dL	191.67 ± 41.71	206.29 ± 52.53	203.84 ± 38.73	198.28 ± 41.37	196.06 ± 54.99	201.54 ± 34.49	0.206
HDL cholesterol, mg/dL	58.11 ± 20.91	55.17 ± 15.75	55.28 ± 18.46	52.52 ± 18.49	52.51 ± 18.50	56.27 ± 16.35	0.175
LDL cholesterol, mg/dL	111.57 ± 34.89	128.47 ± 48.01	127.04 ± 31.67	120.81 ± 35.73	124.46 ± 48.10	124.89 ± 35.30	0.039
AST, U/L	19.50 ± 6.30	23.32 ± 14.23	27.93 ± 17.69	20.49 ± 6.91	21.76 ± 12.26	19.72 ± 5.99	< 0.0001
ALT, U/L	15.82 ± 4.59	16.46 ± 5.38	18.51 ± 5.75	16.46 ± 5.93	16.59 ± 5.74	15.92 ± 5.90	0.031
γGT, U/L	24.63 ± 12.20	33.82 ± 25.96	37.45 ± 38.03	42.71 ± 48.64	28.94 ± 15.17	25.37 ± 16.29	< 0.0001
HOMA	2.00 ± 1.13	3.18 ± 3.49	3.04 ± 2.27	4.04 ± 4.87	2.28 ± 1.07	2.76 ± 2.77	< 0.0001
PTH, pg/mL	84.94 ± 100.37	84.49 ± 170.97	78.37 ± 65.95	86.30 ± 76.75	86.53 ± 95.97	84.83 ± 81.83	0.997
hsCRP, mg/dL	2.58 ± 4.41	2.15 ± 2.79	6.30 ± 13.55	4.30 ± 8.66	3.99 ± 6.42	3.51 ± 4.95	< 0.001
RRI	0.60 ± 0.05	0.59 ± 0.05	0.59 ± 0.04	0.58 ± 0.05	0.59 ± 0.07	0.59 ± 0.06	0.392
EF, %	67.05 ± 8.18	66.94 ± 9.19	65.99 ± 9.15	63.52 ± 12.04	67.15 ± 11.63	66.51 ± 7.26	0.035
E/A	1.15 ± 0.36	1.20 ± 0.26	1.23 ± 0.34	1.09 ± 0.40	1.01 ± 0.26	1.18 ± 0.31	< 0.0001
LVMM/m²	100.48 ± 54.70	105.44 ± 33.79	107.69 ± 48.47	109.21 ± 41.02	110.38 ± 46.63	97.11 ± 28.69	0.179
AMDS	34.94 ± 2.52	34.97 ± 3.03	33.42 ± 3.88	34.23 ± 3.02	34.93 ± 2.68	34.46 ± 3.18	0.005
Homocysteine μmol/L	17.41 ± 3.00	25.53 ± 8.12	28.58 ± 9.23	18.68 ± 9.01	21.26 ± 9.17	18.83 ± 6.25	< 0.0001

BMI: Body mass index; GFR: Glomerular filtration rate; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; γGT: γ-Glutamyl Transpeptidase; hsCRP: High-sensitivity C-reactive protein; RRI: Renal resistive index; EF: Ejection fraction; LVMM: Left ventricular mass myocardial; AMDS: Adherence mediterranean diet score; MTHFR: Methylenetetrahydrofolate reductase; PTH: Parathyroid hormone; HOMA: Homoeostasis model-insulin resistance index.

Table 2 Characteristic of study population and differences between hemodialysis patients and no-hemodialysis n (%)

	Total	Dialysis patients	Patients with maintained	P
	(n = 630)	(n = 160)	Renal function
			(n = 470)
Women	336 (53.3)	72	264	0.014¹
Obese patients	196 (31.1)	24	172	< 0.000¹
Patients with GFR < 90	514 (81.6)	160	354	< 0.000¹
NAFLD patients	256 (40.6)	28	228	< 0.000¹
MTHFR group
Wild genotype	94 (14.9)	36	58	0.016¹
MTHFR C677T	118 (18.7)	28	90
MTHFR 1298 AC	76 (12.1)	20	56
Compound heterozygous C677T and A1298C	158 (25.1)	40	118
MTHFR 1298 CC	80 (12.7)	20	60
MTHFR 677TT	104 (16.5)	16	88
Age, yr	54.60 ± 16.35	67.48 ± 14.57	50.22 ± 14.51	< 0.0001
BMI, kg/m²	27.70 ± 5.76	25.29 ± 3.97	28.52 ± 6.04	< 0.0001
Blood glucose, mg/dL	96.42 ± 26.42	95.33 ± 34.80	96.79 ± 22.91	0.545
Blood urea, mg/dL	52.47 ± 35.74	100.45 ± 41.07	36.13 ± 9.40	< 0.0001
Creatinin, mg/dL	2.36 ± 2.98	6.75 ± 2.99	0.86 ± 0.21	< 0.0001
GFR	62.46 ± 35.32	9.28 ± 3.60	80.56 ± 19.38	< 0.0001
Triglycerides, mg/dL	112.16 ± 64.71	131.90 ± 87.21	105.44 ± 53.48	< 0.0001
Total cholesterol, mg/dL	199.72 ± 44.43	175.80 ± 42.67	207.86 ± 42.05	< 0.0001
HDL cholesterol, mg/dL	54.81 ± 18.10	48.20 ± 15.63	57.07 ± 18.34	< 0.0001
LDL cholesterol, mg/dL	122.75 ± 39.63	101.22 ± 33.04	130.09 ± 39.05	< 0.0001
AST, U/L	21.81 ± 11.16	14.38 ± 4.07	24.34 ± 11.66	< 0.0001
ALT, U/L	16.54 ± 5.63	12.75 ± 4.15	17.83 ± 5.49	< 0.0001
γGT, U/L	33.10 ± 32.11	31.78 ± 19.18	33.55 ± 35.46	0.546
Insulin	11.84 ± 9.73	11.44 ± 10.77	11.98 ± 9.36	0.547
HOMA	3.02 ± 3.30	3.08 ± 3.94	3.00 ± 3.05	0.797
PTH, pg/mL	84.58 ± 105.79	162.38 ± 178.81	57.99 ± 36.85	< 0.0001
hsCRP, mg/dL	3.52 ± 7.01	2.62 ± 2.45	3.82 ± 7.98	0.107
Albumin, g/dL	4.60 ± 0.37	4.64 ± 0.35	4.58 ± 0.37	0.119
Albumin, %	62.39 ± 3.60	62.60 ± 3.03	62.31 ± 3.77	0.388
RRI	0.62 ± 0.06	0.68 ± 0.03	0.60 ± 0.06	< 0.0001
EF,%	65.93 ± 9.99	61.03 ± 12.62	67.87 ± 7.95	< 0.0001
E/A	1.14 ± 0.33	1.03 ± 0.39	1.18 ± 0.30	< 0.0001
LVMM/m²	104.95 ± 42.10	135.37 ± 55.56	93.84 ± 28.91	< 0.0001
AMDS	34.51 ± 3.09	35.93 ± 1.69	34.02 ± 3.31	< 0.0001
Homocysteine, μmol/L	2.1 ± 5.4	36.8 ± 8.5	21.2 ± 7.7	< 0.0001

¹Pearson χ². GFR: Glomerular filtration rate; BMI: Body mass index; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; γGT: γ-Glutamyl transpeptidase; hsCRP: High-sensitivity C-reactive protein; RRI: Renal resistive index; EF: Ejection fraction; LVMM: Left ventricular mass myocardial; AMDS: Adherence mediterranean diet score; MTHFR: Methylenetetrahydrofolate reductase; PTH: Parathyroid hormone; HOMA: Homoeostasis model-insulin resistance index; NAFLD: Non-alcoholic fatty liver disease.

Table 3 Different prevalence of increased renal resistive index, abnormal left ventricular ejection fraction, normal left ventricular relaxation (E/A > 1), and left ventricular hypertrophy (all patients)

	Wild	Heterozygous	Heterozygous	Compound heterozygous	Homozygous	Homozygous	χ²	P
	MTHFR	C677T	A1298C	C677T and A1298C	A1298C	C677T
	(n = 94)	(n = 118)	(n = 76)	(n = 154)	(n = 80)	(n = 104)
high RRI	24	30	16	38	28	22	5.746	0.332
EF < 50%	4	4	4	14	4	0	11.188	0.048
E/A > 1	68	100	66	74	42	70	53.497	< 0.0001
LVH (high LVMM)	12	36	18	44	13	20	14.923	0.011

Pearson χ². MTHFR: Methylenetetrahydrofolate reductase; RRI: Renal resistive index; EF: Ejection fraction; LVMM: Left ventricular mass myocardial; LVH: Left ventricular hypertrophy.

Table 4 Different prevalence of increased renal resistive index, abnormal left ventricular ejection fraction, normal left ventricular relaxation (E/A > 1), and left ventricular hypertrophy (chronic renal failure patients-hemodialysis)

	Wild	Heterozygous	Heterozygous	Compound heterozygous	Homozygous	Homozygous	χ²	P
	MTHFR	C677T	A1298C	C677T and A1298C	A1298C	C677T
	(n = 36)	(n = 28)	(n = 20)	(n = 40)	(n = 20)	(n = 16)
High RRI	20	20	8	28	16	12	10.535	0.061
EF < 50%	4	4	4	12	4	0	9.114	0.105
E/A > 1	24	24	16	8	0	0	72.305	< 0.0001
High LVMM	8	16	4	32	5	4	38.428	< 0.0001

Pearson χ². MTHFR: Methylenetetrahydrofolate reductase; RRI: Renal resistive index; EF: Ejection fraction; LVMM: Left ventricular mass myocardial.

Table 5 Different prevalence of increased renal resistive index, abnormal left ventricular ejection fraction, normal left ventricular relaxation (E/A > 1), and left ventricular hypertrophy (normal renal function patients)

	Wild	Heterozygous	Heterozygous	Compound heterozygous	Homozygous	Homozygous	χ²	P
	MTHFR	C677T	A1298C	C677T and A1298C	A1298C	C677T
	(n = 58)	(n = 90)	(n = 56)	(n = 118)	(n = 62)	(n = 88)
high RRI	4	10	8	10	12	10	6.833	0.233
EF < 50%	0	0	0	2	0	0	5.798	0.326
E/A > 1	44	76	50	66	42	70	19.848	0.001
High LVMM	4	20	14	12	8	16	13.355	0.02

Pearson χ². MTHFR: Methylenetetrahydrofolate reductase; RRI: Renal resistive index; EF: Ejection fraction; LVMM: Left ventricular mass myocardial.

Citation: Trovato FM, Catalano D, Ragusa A, Martines GF, Pirri C, Buccheri MA, Di Nora C, Trovato GM. Relationship of MTHFR gene polymorphisms with renal and cardiac disease. World J Nephrol 2015; 4(1): 127-137
URL: https://www.wjgnet.com/2220-6124/full/v4/i1/127.htm
DOI: https://dx.doi.org/10.5527/wjn.v4.i1.127