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Single-Nucleotide Polymorphisms in Exonic and Promoter Regions of Transcription Factors of Second Heart Field Associated with Sporadic Congenital Cardiac Anomalies

Balkan Journal of Medical Genetics
Volume 24 (2021): Issue 2 (November 2021)
By:
E Wang,  X Fan,  Y Nie,  Z Zheng and  S Hu  
Open Access
|Jun 2022

Figures & Tables

Figure 1

Genotyping of five exonic and promoter SNPs located in GATA5, TBX20, SMYD1 and MEF2C.Genotyping of (A) GATA5: rs6061243 G>C, (B) TBX20: rs336283 A>G, (C) SMYD1: rs1542088 T>G, (D) MEF2C: rs80043958 A>G and (E) GATA5: rs6587239 T>C SNPs by MALDI-TOF-MS.
Genotyping of five exonic and promoter SNPs located in GATA5, TBX20, SMYD1 and MEF2C.Genotyping of (A) GATA5: rs6061243 G>C, (B) TBX20: rs336283 A>G, (C) SMYD1: rs1542088 T>G, (D) MEF2C: rs80043958 A>G and (E) GATA5: rs6587239 T>C SNPs by MALDI-TOF-MS.

Figure 2

Genotyping of the other five SNPs located in GATA5, TBX20, SMYD1 and MEF2C exons and promoters.Genotyping of (A) GATA5: rs41305803 G>A, (B) MEF2C: rs304154 A>G, (C) SMYD1: rs2919881 A>G, (D) TBX20: rs336284 A>G and (E) SMYD1: rs88387557 T>G SNPs by MALDI-TOF-MS.
Genotyping of the other five SNPs located in GATA5, TBX20, SMYD1 and MEF2C exons and promoters.Genotyping of (A) GATA5: rs41305803 G>A, (B) MEF2C: rs304154 A>G, (C) SMYD1: rs2919881 A>G, (D) TBX20: rs336284 A>G and (E) SMYD1: rs88387557 T>G SNPs by MALDI-TOF-MS.

Figure 3

Luciferase assays of MEF2C: rs80043958 A>G, MEF2C: rs304154 A>G, and TBX20: rs336284 A>GFigure 3A, For rs80043958, the plasmid containing the G allele displayed nonsignificant luciferase expression compared with the wild-type A allele (p>0.05). When combined with HLTF, the (G) promoter showed a higher expression level than the (A) promoter (#, p<0.01);Figure 3B, For rs304154, the (G) promoter displayed significant lower luciferase expression than the (A) promoter (π, p<0.01). When the MEF2C promoter was combined with GATA1, FOXC1, or GATA1+FOXC1, the difference was still significant between the two groups ($, λ, †, p<0.01);Figure 3C, For rs336284, the (G) promoter exhibited a significantly lower luciferase expression level than the (A) promoter (§, p<0.01). The promoter (G)+ZFX group also showed a lower expression level (*, p<0.01).
Luciferase assays of MEF2C: rs80043958 A>G, MEF2C: rs304154 A>G, and TBX20: rs336284 A>GFigure 3A, For rs80043958, the plasmid containing the G allele displayed nonsignificant luciferase expression compared with the wild-type A allele (p>0.05). When combined with HLTF, the (G) promoter showed a higher expression level than the (A) promoter (#, p<0.01);Figure 3B, For rs304154, the (G) promoter displayed significant lower luciferase expression than the (A) promoter (π, p<0.01). When the MEF2C promoter was combined with GATA1, FOXC1, or GATA1+FOXC1, the difference was still significant between the two groups ($, λ, †, p<0.01);Figure 3C, For rs336284, the (G) promoter exhibited a significantly lower luciferase expression level than the (A) promoter (§, p<0.01). The promoter (G)+ZFX group also showed a lower expression level (*, p<0.01).

MEF2C: rs304154 A>G

GenotypeTOF (n=105)Control (n=382)OR (95%CI)p value
No(%)No.(%)
AA3331151401
GA5956162421.67(1.03–2.69)0.036
GG131269180.86(0.43–1.74)0.68
GG+GA7269231601.43(0.90–2.26)0.13
AA+GA9288313821
GG13106940.64(0.34–1.21)0.17
A allele12560464611
G allele8540300391.05(0.77–1.44)0.75

MEF2C: rs80043958 A>G

Genotypesimple CHD (n=125)Control (n=381)OR (95%CI)p value
No(%)No.(%)
AA8568294771
GA373084221.52(0.97–2.40)0.07
GG32313.46(0.69–17.45)0.11
GG+GA403287231.59(1.02–2.48)0.04
AA+GA12298378991
GG310343.10(0.62–15.55)0.15
A allele20783672881
G allele431790121.55(1.05–2.30)0.029

TBX20: rs336284 A>G

GenotypeSV (n=34)Control (n=378)OR (95%CI)p value
No(%)No.(%)
AA926131351
GA1441181481.13(0.47–2.68)0.79
GG113266172.42(0.96–6.14)0.06
GG+GA2574247651.47(0.67–3.25)0.33
AA+GA2368312831
GG11106642.26(1.05–4.86)0.033
A allele3247443591
G allele3653313411.59(0.97–2.62)0.07

Patients’ Information

Number(%)
No. of patients (n)383
Age (years)2.22±1.99
Male gender(n, %)216(56%)
Clinical diagnosis (n, %)
  simple CHD125(33%)
    VSD94(25%)
    ASD19(5%)
    PDA12(3%)
  ROVTO223(58%)
    TOF107(28%)
    PA or PS with VSD67(17%)
    PA or PS with IVS49(13%)
  SV35(9%)

Main effects of SNPs on CHD risk

SNPHomozygotes (for common alleles)HeterozygotesHomozygotes (for rarer alleles)
CaseControlCaseControlOR (95%CI)p valueCaseControlOR (95%CI)p value
GATA5: rs6061243 G>C103182200824.31 (3.03–6.13)1.03× 10−16701191.04 (0.71–1.52)0.84
TBX20: rs336283 A>G761121931851.54 (1.08–2.19)0.017109841.91 (1.27–2.87)0.002
SMYD1: rs1542088 T>G29231083731.21 (0.85–1.72)0.360––
MEF2C: rs80043958 A>G28029496831.21 (0.87–1.70)0.26531.75 (0.41–7.39)0.44
GATA5: rs6587239 T>C88901962030.99 (0.69–1.41)0.9496881.12 (0.74–1.69)0.6
GATA5: rs41305803 G>A1281471881781.21 (0.89–1.66)0.2362581.23 (0.78–1.89)0.35
MEF2C: rs304154 A>G1341511881621.31 (0.96–1.79)0.0958690.95 (0.62–1.44)0.8
SMYD1: rs2919881 A>G2572501061160.89 (0.65–1.22)0.4718161.09 (0.55–2.19)0.8
TBX20: rs336284 A>G1261311691810.97 (0.70–1.34)0.8677661.21 (0.81–1.83)0.36
SMYD1: rs88387557 T>G35035731241.32 (0.76–2.29)0.33111.02 (0.06–16.37)1
DOI: https://doi.org/10.2478/bjmg-2021-0028 | Journal eISSN: 2199-5761
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Language: English
Page range: 39 - 47
Published on: Jun 5, 2022
Published by: Macedonian Academy of Sciences and Arts
In partnership with: Paradigm Publishing Services
Publication frequency: 2 issues per year
Keywords:
Polymorphisms,
Transcription factor,
Congenital cardiac anomaly
Related subjects:
Medicine,
Basic medical science,
Basic medical science, other

© 2022 E Wang, X Fan, Y Nie, Z Zheng, S Hu, published by Macedonian Academy of Sciences and Arts
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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