Association of the MTHFR C677T (rs1801133) polymorphism with idiopathic male infertility in a local Pakistani population

M Irfan; M Ismail; M Azhar Beg; A Shabbir; A Rashid Kayani; G Kaukab Raja

doi:10.1515/bjmg-2016-0007

Table 1

Allele frequencies of the MTHFR C677T mutation in the studied subjects.

Patient Group	Allele	Infertile Men n (%)	Fertile Men n (%)	OR (95% CI)	p Value	AOR (95% CI)	p Value
Azoospermic	C T	90 (78.95) 24 (21.05)	404 (92.66) 32 (7.34)	1 3.37 (1.89-5.99)	0.000	1 2.05 (1.14-3.70)	0.017aa
Oligospermic	C T	95 (71.97) 37 (28.03)	404 (92.66) 32 (7.34)	1 4.92 (2.91-8.30)	0.000	1 4.36 (2.52-7.53)	0.000aa
Asthenozoospermic	C T	64 (72.73) 24 (27.27)	404 (92.66) 32 (7.34)	1 3.70 (2.09-6.52)	0.000	1 3.70 (1.98-6.89)	0.001aa
Teratozoospermic	C T	41 (70.69) 17 (29.31)	404 (92.66) 32 (7.34)	1 5.23 (2.68-10.23)	0.000	1 3.31 (1.61-6.82)	0.000aa
OAT	C T	29 (72.50) 11 (27.50)	404 (92.66) 32 (7.34)	1 2.39 (1.14-5.03)	0.021	1 3.33 (1.37-8.07)	0.008aa
Infertile normospermic	C T	387 (87.56) 55 (12.44)	404 (92.66) 32 (7.34)	1 0.90 (0.61-1.32)	0.581	1 1.77 (1.10-2.85)	0.018aa
Total infertile subjects	C T	706 (80.78) 168 (19.22)	404 (92.66) 32 (7.34)	1 1.50 (1.10-2.05)	0.012	1 2.12 (1.38-3.92)	0.016aa

OR: odds ratio; 95% CI: 95% confidence interval; AOR: odds ratio adjusted for age, body mass index (BMI), occupation, working shift and hours; C: wild type; T: mutated; OAT: oligoasthenoteratospermic.

aa A p value of <0.05 was considered to be significant.

Table 2

Genotype frequencies of the MTHFR C677T mutation in the studied subjects.

Patient Group	Genotype	Infertile Men n (%)	Fertile Men n (%)	OR (95% CI)	p Value	AOR (95% CI)	p Value
Azoospermic	CC CT TT CT + TT	36 (63.16) 18 (31.58) 3 (5.26) 21 (36.84)	187 (85.78) 30 (13.76) 1 (0.46) 31 (14.22)	1 3.12 (1.57-6.186) 15.58 (1.58-154.06) 3.52 (1.82-6.80)	0.001 0.019 0.000	1 2.59 (1.27-5.30) 13.30 (1.23-33.20) 2.12 (1.09-4.15)	0.009aa 0.033aa 0.027aa
Oligospermic	CC CT TT CT + TT	34 (51.52) 27 (40.91) 5 (7.58) 32 (48.48)	187 (85.78) 30 (13.76) 1 (0.46) 31 (14.22)	1 4.95 (2.62-9.35) 27.50 (3.12-242-77) 5.58 (3.07-10.49)	0.000 0.003 0.000	1 4.33 (2.18-8.59) 24.05 (2.54-87.34) 5.01 (2.58-9.71)	0.000aa 0.006aa 0.000aa
Asthenozoospermic	CC CT TT CT + TT	22 (50.00) 20 (45.45) 2 (4.55) 22 (50.00)	187 (85.78) 30 (13.76) 1 (0.46) 31 (14.22)	1 5.67 (2.76-11.62) 17.00 (1.48-195.20) 6.03 (2.99-12.18)	0.000 0.023 0.000	1 5.10 (2.32-11.23) 15.93 (1.22-97.81) 5.03 (2.35-10.75)	0.000aa 0.035aa 0.000aa
Teratozoospermic	CC CT TT CT + TT	15 (51.72) 11 (37.39) 3 (10.34) 14 (48.28)	187 (85.78) 30 (13.76) 1 (0.46) 31 (14.22)	1 4.57 (1.92-10.89) 37.40 (3.66-381-91) 5.63 (2.48-12.80)	0.000 0.002 0.000	1 2.90 (1.09-7.76) 30.99 (2.91-82.3) 3.17 (1.27-7.91)	0.033aa 0.004aa 0.014aa
OAT	CC CT TT CT + TT	10 (50.00) 9 (45.00) 1 (5.00) 10 (50.00)	187 (85.78) 30 (13.76) 1 (0.46) 31 (14.22)	1 5.61 (2.12-14.94) 18.70 (1.09-321.32) 6.03 (2.32-15.68)	0.000 0.044 0.000	1 4.10 (0.23-13.19) 14.68 (0.61-68.20) 4.55 (1.46-14.14)	0.018aa 0.098 0.009aa
Infertile normospermic	CC CT TT CT + TT	168 (76.02) 51 (23.08) 2 (0.90) 53 (23.98)	187 (85.78) 30 (13.76) 1 (0.46) 31 (14.22)	1 1.89 (1.15-3.12) 2.23 (0.20-24.77) 1.90 (1.17-3.12)	0.012 0.515 0.010	1 1.92 (1.12-3.27) 2.48 (0.22-28.28) 1.95 (1.17-3.26)	0.017aa 0.464 0.011aa
Total infertile subjects	CC CT TT CT + TT	285 (65.22) 136 (31.12) 16 (3.66) 152 (34.78)	187 (85.78) 30 (13.76) 1 (0.46) 31 (14.22)	1 2.97 (1.92-4.60) 10.50 (1.38-79.83) 3.22 (2.10-4.94)	0.000 0.023 0.000	1 1.81 (1.17-2.80) 9.24 (1.20-70.92) 2.01 (1.31-3.08)	0.008aa 0.032aa 0.001aa

OR: odds ratio; 95% CI: 95% confidence interval; AOR: odds ratio adjusted for age, body mass index (BMI), occupation, working shift and hours; C: wild type; T: mutated; OAT: oligoasthenoteratospermic.

aa A p value of <0.05 was considered to be significant.

Table 3

Allelic distribution of the MTHFR C677T mutation in infertile patients and controls from various other populations.

Study	Country	Patients	Controls	Patients		Controls		OR	SE	Lower Limit	Upper Limit	p Value
[Refs.]		n	n	C	T (%)	C	T (%)	OR	SE	Lower Limit	Upper Limit	p Value
African
[18]	Egypt	139	90	133	125 (48.45)	126	54 (30.00)	2.19	0.20	1.47	3.28	0.000aa
[19]	Egypt	107	107	163	51 (23.83)	156	58 (27.10)	0.84	0.22	0.54	1.30	0.438
[20]	Algeria	74	84	95	55 (36.67)	110	58 (35.52)	1.10	0.23	0.69	1.74	0.690
[21]	Morocco	344	690	523	165 (23.98)	988	392 (28.41)	0.80	0.11	0.64	0.98	0.033
Asian
[22]	China	182	53	140	224 (61.54)	58	48 (45.28)	1.93	0.22	1.25	2.99	0.003aa
[23]	China	355	252	420	290 (40.85)	351	153 (30.36)	1.58	0.12	1.24	2.02	0.000aa
[24]	China	75	72	92	58 (38.67)	108	36 (25.00)	1.89	0.26	1.15	3.12	0.013aa
[25]	China	82	133	64	100 (60.98)	133	133 (50.00)	1.56	0.20	1.05	2.32	0.027aa
[26]	China	131	293	125	139 (52.65)	338	248 (42.32)	1.52	0.15	1.13	2.03	0.005aa
[27]	China	290	90	216	364 (62.76)	95	85 (47.22)	1.88	0.17	1.34	2.64	0.000aa
[28]	China	271	180	262	280 (51.66)	149	211 (58.61)	0.75	0.14	0.58	0.99	0.040aa
[29]	India	151	200	250	52 (17.22)	363	37 (9.25)	2.04	0.23	1.30	3.20	0.002aa
[30]	India	522	315	872	172 (16.48)	560	70 (11.11)	1.58	0.15	1.17	2.12	0.003aa
[31]	India	12	20	13	11 (45.83)	37	3 (7.50)	10.44	0.73	2.51	43.37	0.001aa
[32]	India	637	364	1048	226 (17.74)	627	99 (13.64)	1.37	0.13	1.06	1.76	0.017aa
[33]	India	206	230	358	54 (13.11)	418	42 (9.13)	1.50	0.22	0.98	2.30	0.062
[34]	India	179	200	239	119 (33.24)	240	160 (40.00)	0.75	0.15	0.55	1.01	0.054
[35]	India	100	100	186	14 (7.00)	181	19 (9.50)	0.72	0.37	0.35	1.47	0.365
[36]	Iran	164	328	196	132 (40.24)	436	220 (33.54)	1.33	0.14	1.01	1.67	0.039aa
[37]	Iran	118	132	161	75 (31.78)	206	58 (21.97)	1.65	0.20	1.11	2.47	0.014aa
[38]	Iran	242	255	327	157 (32.44)	386	124 (24.31)	1.49	0.14	1.13	1.97	0.005aa
[39]	Iran	266	77	402	130 (24.44)	74	80 (51.95)	0.30	0.19	0.21	0.43	0.100
[40]	Iran	300	303	430	170 (28.33)	426	180 (29.70)	0.94	0.13	0.73	1.20	0.600
[41]	Korea	371	396	410	332 (44.73)	490	302 (38.13)	1.31	0.10	1.07	1.61	0.009aa
[42]	Korea	360	325	411	309 (42.92)	402	248 (38.15)	1.22	0.11	0.98	1.51	0.073
[43]	Korea	85	246	104	66 (38.82)	280	212 (43.09	0.84	0.18	0.59	1.20	0.332
Caucasian
[44]	Brazil	156	233	222	90 (28.85)	387	79 (16.95)	1.99	0.18	1.41	2.80	0.000aa
[45]	Brazil	133	173	183	83 (68.80)	299	47 (13.85)	2.89	0.21	1.93	4.31	0.000aa
[46]	Slovenia	100	111	109	91 (45.50)	144	78 (35.14)	1.54	0.20	1.04	2.28	0.030aa
[47]	Italy	59	46	54	64 (54.24)	57	35 (38.04)	1.93	0.28	1.11	3.36	0.020aa
[48]	Italy	93	105	111	75 (40.32)	119	91 (43.33)	0.88	0.20	0.59	1.32	0.545
[49]	Turkey	100	50	132	68 (34.00)	80	20 (20.00)	2.06	0.29	1.16	3.65	0.013aa
[50]	Germany	255	200	321	189 (37.09)	273	127 (31.75)	1.27	0.14	0.96	1.67	0.095
[51]	The Netherlands	77	113	112	42 (27.27)	148	78 (34.51)	0.71	0.23	0.45	1.11	0.137
[52]	Serbia	52	56	68	36 (34.62)	72	40 (35.71)	0.95	0.29	0.54	1.67	0.866
[53]	Poland	284	352	399	169 (29.75)	482	222 (31.53)	0.92	0.12	0.72	1.17	0.494
[54]	Jordan	150	150	197	103 (34.33)	215	85 (28.33)	1.32	0.18	0.97	1.87	0.114
[55]	Sweden	149	182	209	89 (29.87)	261	103 (28.30)	1.08	0.17	0.77	1.51	0.658
[56]	France	250	114	337	163 (32.00)	150	78 (34.21)	0.93	0.17	0.67	1.30	0.668
[57]	Russia	180	301	250	110 (30.56)	421	181 (30.07)	1.02	0.14	0.77	1.36	0.873
[58]	Canada	39	19	58	20 (51.22)	21	17 (44.74)	0.43	0.42	0.19	0.96	0.041aa

OR: odds ratio; SE: standard error.

aa A p value of <0.05 was considered to be significant.

Table 4

Genetic distribution of the MTHFR C677T mutation in infertile patients and controls from various other populations.

Study	Country	Patients	Controls	Patients		Controls		OR	SE	Lower Limit	Upper Limit	P Value
[Refs.]		n	n	CC	CT + TT (%)	CC	CT + TT (%)	OR	SE	Lower Limit	Upper Limit	P Value
African
[18]	Egypt	139	90	109	133 (54.96)	144	111 (43.53)	1.58	0.18	1.11	2.26	0.011aa
[19]	Egypt	107	107	55	84 (60.43)	41	49 (54.44)	1.28	0.27	0.75	2.18	0.370
[20]	Algeria	74	84	31	43 (58.11)	36	48 (57.14)	1.04	0.32	0.55	1.96	0.902
[21]	Morocco	344	690	199	145 (42.15)	351	339 (49.13)	0.75	0.13	0.58	0.98	0.034aa
Asian
[22]	China	182	53	27	155 (85.16)	15	38 (71.70)	2.27	0.37	1.10	4.67	0.027aa
[23]	China	355	252	130	225 (63.38)	128	124 (49.21)	1.79	0.17	1.29	2.48	0.001aa
[24]	China	75	72	27	48 (64.00)	40	32 (44.44)	2.22	0.34	1.15	4.31	0.018aa
[25]	China	82	133	14	68 (82.93)	36	97 (72.93)	1.80	0.35	0.90	3.60	0.095
[26]	China	131	293	35	97 (73.48)	98	293 (74.94)	0.93	0.23	0.59	1.45	0.741
[27]	China	290	90	39	251 (86.55)	24	66 (73.33)	2.34	0.29	1.32	4.16	0.004aa
[28]	China	271	180	75	196 (72.32)	32	148 (82.22)	0.57	0.24	0.35	0.90	0.016aa
[29]	India	151	200	105	46 (30.46)	163	37 (18.50)	1.93	0.25	1.17	3.17	0.010aa
[30]	India	522	315	378	144 (27.59)	251	64 (20.32)	1.49	0.17	1.07	2.09	0.019aa
[31]	India	12	20	4	8 (66.67)	18	2 (10.00)	18.00	0.96	2.72	19.23	0.003aa
[32]	India	637	364	447	190 (29.83)	275	89 (24.45)	1.31	0.15	0.98	1.76	0.068
[33]	India	206	230	158	48 (23.30)	188	42 (18.26)	1.36	0.24	0.85	2.16	0.195
[34]	India	179	200	81	98 (54.75)	70	130 (65.00)	0.65	0.21	0.43	0.99	0.042aa
[35]	India	100	100	86	14 (14.00)	81	19 (19.00)	0.69	0.38	0.33	1.48	0.342
[36]	Iran	164	328	58	106 (64.63)	144	184 (56.10)	1.43	0.20	0.97	2.11	0.070
[37]	Iran	118	132	51	67 (56.78)	77	55 (41.67)	1.84	0.26	1.11	3.04	0.017aa
[38]	Iran	242	255	109	133 (54.96)	144	111 (43.53)	1.58	0.18	1.11	2.26	0.011aa
[39]	Iran	266	77	153	113 (42.48)	33	44 (57.14)	0.55	0.26	0.33	0.92	0.024aa
[40]	Iran	300	303	161	139 (46.33)	151	152 (50.17)	0.86	0.16	0.62	1.18	0.347
[41]	Korea	371	396	103	268 (72.24)	145	251 (63.38)	1.50	0.16	1.11	2.04	0.009aa
[42]	Korea	360	325	115	245 (68.06)	118	207 (63.69)	1.21	0.16	0.88	1.67	0.229
[43]	Korea	85	246	30	55 (64.71)	87	159 (64.63)	1.00	0.26	0.60	1.68	0.990
Caucasian
[44]	Brazil	156	233	81	75 (48.08)	167	66 (28.33)	2.34	0.22	1.53	3.58	0.000aa
[45]	Brazil	133	173	66	67 (50.38)	136	37 (21.39)	3.73	0.25	2.27	6.14	0.000aa
[46]	Slovenia	100	111	29	71 (71.00)	47	64 (57.66)	1.80	0.29	1.01	3.19	0.045aa
[47]	Italy	59	46	11	48 (81.36)	18	28 (60.87)	2.81	0.45	1.16	6.78	0.022aa
[48]	Italy	93	105	37	56 (60.22)	43	62 (59.05)	1.05	0.29	0.59	1.85	0.867
[49]	Turkey	100	50	44	56 (56.00)	30	20 (40.00)	1.91	0.35	0.96	3.81	0.066
[50]	Germany	255	200	114	141 (55.29)	92	108 (54.00)	1.05	0.19	0.73	1.53	0.783
[51]	The Netherlands	77	113	42	35 (45.45)	50	63 (55.75)	0.66	0.30	0.37	1.18	0.164
[52]	Serbia	52	56	22	30 (57.69)	23	33 (58.93)	0.95	0.39	0.44	2.04	0.896
[53]	Poland	284	352	143	256 (64.16)	166	316 (65.56)	0.94	0.14	0.71	1.24	0.665
[54]	Jordan	150	150	67	83 (55.33)	74	76 (50.67)	1.21	0.23	0.77	1.90	0.418
[55]	Sweden	149	182	73	76 (51.01)	94	88 (48.35)	1.11	0.22	0.72	1.72	0.631
[56]	France	250	114	118	132 (52.80)	49	65 (57.02)	0.84	0.23	0.54	1.32	0.454
[57]	Russia	180	301	89	91 (50.56)	153	148 (49.17)	1.06	0.19	0.73	1.53	0.769
[58]	Canada	39	19	22	17 (43.59)	8	11 (57.89)	0.56	0.57	0.19	1.70	0.308

OR: odds ratio; SE: standard error.

aa A p value of <0.05 was considered to be significant.

Association of the MTHFR C677T (rs1801133) polymorphism with idiopathic male infertility in a local Pakistani population

Figures & Tables

Table 1

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Table 4

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