Association of Maternal Regulatory Single Nucleotide Polymorphic CD99 Genotype with Preeclampsia in Pregnancies Carrying Male Fetuses in Ethiopian Women

Abstract

Preeclampsia (PE) is a human specific syndrome with unknown etiology causing maternal and fetal morbidities and mortalities. In PE, maternal inflammatory responses are more exaggerated if the fetus is male than female. Other pregnancy complications such as spontaneous abortions are also more common if the fetus is male. Recent transcriptome findings showed an increased expression of CD99 in erythroid cells from male cord blood in PE. The single nucleotide polymorphism (SNP) rs311103, located in a GATA-binding site in a regulatory region on the X/Y chromosomes, governs a coordinated expression of the Xg blood group members CD99 and Xga in hematopoietic cells in a sex-dependent fashion. The rs311103C disrupts the GATA-binding site, resulting in decreased CD99 expression. We aimed to investigate the association between PE and the allele frequency of rs311103 in pregnancies in a fetal sex-dependent fashion. In a case-controlled study, we included 241 pregnant women, i.e., 105 PE cases and 136 normotensive controls. A SNP allelic discrimination analysis was performed on DNA from maternal venous blood and fetal cord blood by qPCR. A statistically significant association was observed between rs311103 allele frequency and PE in mothers carrying male fetuses. Therefore, the rs311103 genotype may play a role in the pathogenesis of PE in a fetal sex-specific manner.

Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in gestational diabetes mellitus

“…CEBPB (CCAAT enhancer binding protein beta) [38], ACSL4 [39], MBD2 [40], ULK1 [41], NUCB2 [42], TWIST1 [43], HOOK2 [44], CLDN7 [45], TBK1 [46], YIPF6 [47], TFRC (transferrin receptor) [48], ENPP2 [49], SLIT2 [50], MFGE8 [51], FAT1 [52], GPC4 [53], COL6A3 [54], EGFL6 [55], AOC3 [56], CCN2 [57], LYVE1 [58], RARA (retinoic acid receptor alpha) [59], COL18A1 [60], THY1 [61], CD36 [62], PEMT (phosphatidylethanolamine N-methyltransferase) [63], AIF1L [64], OXTR (oxytocin receptor) [65], LMNA (lamin A/C) [66], CXCL14 [67], DKK3 [68], ANGPTL2 [69] and CMTM7 [70] were reported to be associated with obesity, but these genes might be linked with progression of GDM. AHR (aryl hydrocarbon receptor) [71], STS (steroid sulfatase) [72], PLAC1 [73], CYP11A1 [74], PSG11 [75], STAT5B [76], TLR3 [77], FOLR1 [78], HSPB1 [79], HSP90AA1 [80], ANXA4 [81], ATF3 [82], DAPK1 [83], ENTPD1 [84], ABL1 [85], VSIG4 [86], CD99 [87], VWF (von Willebrand factor) [88], PODXL (podocalyxin like) [89], PDPN (podoplanin) [90], RND3 [91], VCAN (versican) [92], AXL (AXL receptor tyrosine kinase) [93], PIEZO1 [94], GAS6 [93], LAMA4 [95], CAV1 [96], DLL1 [97], CD44 [98], CD81 [99], SMAD3 [100], NES (nestin) [101], DCN (decorin) [102], AGTR1 [103], SLIT3 [104], B2M [105], STAT3 [106], STC1 [107] and ADAMTS1 [108] were shown to participate in facilitating the preeclampsia. Majchrzak-Celiń ka et al [109] ...…”

Solving the Puzzle of Global Health Inequity: Completing the Picture Piece by Piece by Piece

“…The importance of contextualizing programs, interventions, and technologies was highlighted in publications that provided contributions and insights regarding the development of an evidence-based answer to the third foundational research question. Variations in genotypes among population groups, for example, can have significant implications for treatment in areas such as breast cancer (Hadgu et al, 2020 ) and preeclampsia (Kelemu et al, 2020a , 2020b ). Important differences also exist in the prevalence of chronic kidney disease (CKD; Molla et al, 2020 ), abnormal glucose tolerance (Hobabagabo et al, 2020 ), and in-hospital mortality rates for older adults (Orikiriza et al, 2020 ).…”

“…Characteristics of individuals: Self-efficacy What interventions and technologies are key to eradicating global health inequities? •Interventions and devices must fit local contexts •Appropriate funding is essential •Barriers to service provision must be understood •Public messaging with ongoing evaluative research can maximise behaviour change Hadgu et al ( 2020 ), Kelemu et al ( 2020a , 2020b ), Molla et al ( 2020 ), Hobabagabo et al ( 2020 ), Orikiriza et al ( 2020 ), Chandler et al ( 2020 ), Carey and Gullifer ( 2020a ), *Leckning et al ( 2020 ), Carey et al ( 2020a , 2020b ), Iverson et al 2020 ), HIrschhorn et al ( 2020 ), Wotton and Binagwaho ( 2020 ), Isano et al ( 2020 ), Louis et al ( 2020 ), Lazarus et al ( 2020b ), Ratzan et al ( 2020 ), *Nduwayezu et al ( 2020 ), Harrington et al ( 2020 ), Forrester et al ( 2020 ), Atun et al ( 2020 ), Semret et al ( 2020 ), *Ndayambaje et al ( 2020 ), Chu et al ( 2020 ), Kediso et al ( 2020 ), Tuasha et al ( 2020 ), Owolabi et al ( 2020a , 2020b ), Karangwa et al ( 2020 ), Carey and Gullifer ( 2020b ), Landrigan et al ( 2020 ), Binagwaho et al ( 2020 ) I. Intervention characteristics: Adaptability; complexity; cost II.…”

The Sexually Dimorphic Nature of the Human Placenta: A Literature Review

“…Male fetuses are 20% more likely to experience poorer outcomes, such as increased rates of death in early gestation [3,29]. For women with preeclampsia, maternal inflammatory responses are more exaggerated in male fetuses [30]. Such obstetric outcomes are the result of complex interactions between the mother, fetus, and the placenta in a sex-dependent fashion.…”