gene mutations and pregnancy induced hypertension: a meta
TRANSCRIPT
White
Learning Objectives ---- At the end of this presentation the learner will be able to:
1. Understand MTHFR C677T gene mutations in relation to pregnancy induced hypertension (PIH) in various race-ethnicity groups in the world. 2. Discuss potential epigenetic factors associated with PIH.
Gene Mutations and Pregnancy Induced Hypertension: A Meta-Analysis Ya-Ling Yang, RN, Ph.D. 1; Shyang-Yun Pamela K. Shiao, PhD, RN, FAAN 2
1 School of Nursing, College of Medicine, National Taiwan University. 2 College of Nursing, Georgia Regents University.
Objectives
To disseminate current evidence on population genome
health and related epigenetic factors, through the meta-
analyses of methylenetetrahydrofolate reductase (MTHFR)
gene in pregnant women who developed hypertension.
Background
PIH including preeclampsia, eclampsia are the leading
causes of maternal and perinatal mortalities.
Genetic and environmental factors contribute to its
development.
Many studies have reported the association between the
MTHFR gene C677T polymorphism and risk of PE, but the
results were inconclusive.
Methods
Cochrane, Embase, PubMed, and Web of Science on-line
databases were searched using related key words.
Progression on Selection of Studies
Presentation at the 43rd Biennial Convention, Honor Society of Nursing, Sigma Theta Tau International, November 7 – 11, 2015, Las Vegas, Nevada, USA.
Potentially relevant studies identified and
screened for retrieval (n = 73)
16 meta-analyses
57 case control studies
9 studies excluded (not English):
2 meta-analyses
7 case control studies
Studies retrieved for more detail evaluations (n = 64)
14 meta-analyses
51 case control studies
14 meta-analyses included:
43 case control studies (16 overlapping; 8
without sufficient information)
Studies with sufficient information fulfilling all inclusion/ exclusion criteria
(n = 52, 2 studies with 3 and 2 additional race groups, respectively)
51 case control studies:
14 papers without sufficient information; 4
papers not focus on pregnancy hypertension
Results Pool Relative Risk of MTHFR 677 Gene Subtypes (57 studies)
Genotype
(number of studies)
PIH Case
N=6463 (n, %)
Control
N=11213 (n, %)
RR (95% CI)
TT Overall (57) 822 (12.72) 1179 (10.51) 1.26 (1.11 – 1.40)***
White (24) 357 (11.86) 610 ( 9.69) 1.16 (1.01 – 1.34)*
Hispanic (4) 236 (21.91) 346 (23.63) 0.98 (0.85 – 1.13)
South American (4) 62 (16.40) 66 (11.89) 1.40 (1.01 – 1.93)*
East Asia (8) 153 (26.15) 163 (13.55) 1.82 (1.49 – 2.23)***
South Asia (5) 16 ( 2.78) 31 ( 3.12) 0.96 (0.51 – 1.84)
Middle Eastern (6) 53 ( 8.31) 38 ( 7.29) 1.16 (0.77 – 1.74)
Africa (6) 20 ( 2.70) 2 ( 0.26) 5.82 (2.06 – 16.5)***
CT Overall (57) 2437 (37.71) 4402 (39.25) 1.00 (0.96 – 1.04)
White (24) 1254 (41.66) 2614 (41.53) 1.01 (0.96 – 1.07)
Hispanic (4) 464 (43.08) 629 (42.96) 1.03 (0.94 – 1.13)
South American (4) 173 (45.77) 258 (46.49) 0.94 (0.81 – 1.08)
East Asia (8) 272 (46.50) 69 ( 4.56) 0.96 (0.86 – 1.07)
South Asia (5) 97 (16.87) 200 (20.12) 0.77 (0.61 – 0.98)*
Middle Eastern (6) 244 (38.24) 185 (35.51) 1.06 (0.92 – 1.24)
Africa (6) 142 (19.16) 152 (19.44) 1.07 (0.88 – 1.30)
CC Overall (57) 3204 (49.57) 5632 (50.22) 0.96 (0.93 – 1.00)
White (24) 1399 (46.48) 3069 (48.76) 0.96 (0.91 –1.01)
Hispanic (4) 377 (35.00) 489 (33.40) 0.98 (0.88 – 1.08)
South American (4) 143 (37.83) 231 (41.62) 0.96 (0.81 – 1.13)
East Asia (8) 160 (27.35) 451 (37.49) 0.74(0.64 – 0.86)***
South Asia (5) 462 (80.35) 763 (76.76) 1.06 (0.95 – 1.17)
Middle Eastern (6) 341 (53.45) 298 (57.20) 0.94 (0.85 – 1.04)
Africa (6) 579 (78.14) 628 (80.31) 0.95 (0.91 – 1.00)
CI = Confidence Interval; P value = *<0.05, ***<0.001
TT + CT subtypes by Country-Race for Case and Control groups (# of studies; # of subjects)
0
0
1
0
0
4
0
4
0
5
11
5
11
13
11
8
13
11
10
14
19
7
13
0
17
16
22
19
8
31
0
11
16
17
19
21
33
32
39
39
36
43
39
38
40
43
39
41
42
39
39
51
48
64
48
51
47
50
61
47
0 10 20 30 40 50 60 70 80
Afro-Caribbean (1, 7)
South Africa (2, 448)
Sri Lanka (1, 171)
Zimbabwe (1, 183)
Indonesia (1, 27)
India (2, 793)
Asian mixeed (1, 3)
Iran (2, 297)
Tunisia (1, 100)
Finland (3, 890)
Brazil (2, 228)
Slovak (1, 40)
UK (3, 190)
USA (4, 599)
Turkey (4, 224)
Denmark (1, 1842)
Croatia (1, 38)
Austria (1, 1397)
Netherland (3, 680)
Australia (1, 79)
Germany (2, 113)
Hungary (2, 174)
Japan (4, 910)
Egypt (1, 44)
Peru (1, 177)
China (4, 293)
Spain (1, 122)
Italy (1, 129)
Ecuador (1, 150)
Mexico (4, 865)
ct 677 tt% ct 677 ct%
0
0
2
1
2
3
7
6
5
6
18
18
11
14
12
12
8
8
13
12
9
12
23
34
20
31
19
30
12
30
21
15
21
16
15
15
21
34
45
35
37
39
39
39
45
45
48
56
45
42
48
47
45
45
50
48
56
44
49
48
0 10 20 30 40 50 60 70 80
Afro-Caribbean (1, 28)
South Africa (2, 454)
Sri Lanka (1, 175)
Zimbabwe (1, 171)
Indonesia (1, 41)
India (2, 345)
Asian mixeed (1, 14)
Iran (2, 390)
Tunisia (1, 44)
Finland (3, 494)
Brazil (2, 105)
Slovak (1, 28)
UK (3, 388)
USA (4, 541)
Turkey (4, 248)
Denmark (1, 263)
Croatia (1, 25)
Austria (1, 25)
Netherland (3, 583)
Australia (1, 156)
Germany (2, 86)
Hungary (2, 284)
Japan (4, 353)
Egypt (1, 44)
Peru (1, 123)
China (4, 232)
Spain (1, 43)
Italy (1, 94)
Ecuador (1, 150)
Mexico (4, 536)
PIH 677 tt% PIH 677 ct%
East Asia
Xt Xc Nt Nc
18 11 34 102
34 32 99 192
12 33 89 182
16 40 51 318
18 9 62 51
17 11 25 53
20 9 33 40
18 18 39 102
Africa
Xt Xc Nt Nc
15 0 29 44
0 0 28 7
2 0 42 100
1 0 104 110
1 2 348 336
1 0 170 183
Xt Xc Nt Nc
14 32 234 643
12 6 121 106
4 7 109 96
31 143 232 1699
7 15 64 64
1 7 14 27
31 12 252 88
11 9 79 81
1 0 14 1
32 11 227 109
21 36 146 367
20 19 137 138
5 2 23 38
2 5 23 33
8 6 112 95
25 6 139 67
2 155 23 1242
28 24 66 105
8 27 35 95
19 11 137 68
13 15 14 15
19 14 104 100
33 41 248 319
10 7 100 88
Conclusion
MTHFR 677 homozygous (TT) mutation genotype was significantly
associated with increased risk of developing PIH (p < 0.001).
MTHFR 677TT subtype was a significant risk of PIH in White race (RR= 1.16, p
< 0.05), South American (RR=1.40, p < 0.05), East Asian (RR= 1.82, p < 0.001)
and in Africa (RR=5.82, p < 0.001) .
Lifestyle factors, body mass index (BMI) before pregnancy (Kg/M2) was an
important predictor for the development of PIH.
Normal weight (BMI < 25) was protective against the development of PIH and
preeclampsia (RR = 0.75, p < 0.0001); whereas, overweight (BMI = 25-29, RR =
1.52, p < 0.0001) and obesity (BMI > 30, RR = 1.80, p < 0.0001) were
associated with increased risk of developing PIH and preeclampsia (376
cases and 2294 controls in 2 studies of Caucasian women).