Gene polymorphisms within regions of complement component C1q in HIV associated preeclampsia
Sumeshree Govender1, Nihar R Nayak2, Louansha Nandlal1
1Optics and Imaging Centre, Doris Duke Medical Research Institute, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
Insights
Single nucleotide polymorphisms (SNPs) in the C1q gene are not linked to preeclampsia (PE) in African ancestry women. However, the C1q rs292001 GA genotype may influence PE susceptibility, particularly with HIV infection.
Area of Science:
- Immunogenetics
- Reproductive Medicine
- Infectious Diseases
Background:
- Preeclampsia (PE) is a pregnancy complication with complex etiology.
- The complement system, particularly C1q, plays a role in immune regulation and may be implicated in PE pathogenesis.
- Human immunodeficiency virus (HIV) infection can alter immune responses and potentially interact with PE development.
Purpose of the Study:
- To investigate the association between C1q gene polymorphisms (rs292001 and rs294183) and preeclampsia in women of African ancestry.
- To explore potential interactions between these C1q gene variants, HIV infection, and preeclampsia risk.
Main Methods:
- A case-control study involving 325 pregnant women of African ancestry.
- Participants were categorized into normotensive and preeclamptic groups, with further stratification by HIV status (infected vs. uninfected).
- Genotyping for C1q SNPs rs292001 and rs294183 was performed using a TaqMan® SNP Genotyping assay.
Main Results:
- No significant differences in allelic or genotype frequencies for C1q rs292001 and rs294183 were found between preeclamptic and normotensive women.
- No significant associations were observed between these SNPs and preeclampsia, regardless of HIV status.
- A potential role for the heterozygous GA genotype at C1q rs292001 was suggested, with an odds ratio of 1:2 in preeclamptic women.
Conclusions:
- C1q gene polymorphisms rs292001 and rs294183 are not directly associated with preeclampsia development in women of African ancestry.
- The C1q rs292001 heterozygous GA genotype may confer susceptibility to preeclampsia, irrespective of HIV status.
- This finding suggests potential dysregulation of C1q, impacting complement function and immune responses in HIV-positive women with preeclampsia.
Objective:
This study investigates the association of C1q gene (rs292001 and rs294183) polymorphisms in HIV infected and uninfected preeclamptic women of African ancestry.
Materials And Methods:
The study population consisted of 325 pregnant women of African ancestry grouped into 145 normotensive pregnant women (72 HIV uninfected normotensive, 73 HIV infected normotensive) and 180 preeclamptic pregnant women (103 HIV uninfected preeclamptics, 77 HIV infected preeclamptics). Preeclamptic pregnant women were further sub-grouped into 79 early-onset preeclampsia (EOPE) (40 HIV uninfected EOPE, 39 HIV infected EOPE) and 101 late-onset preeclampsia (LOPE) (63 HIV uninfected LOPE, 38 HIV infected LOPE). Genotyping of complement C1q gene polymorphisms (rs292001 and rs294183) was detected using a TaqMan® SNP Genotyping assay from purified DNA.
Results:
No significant differences in allelic and genotype frequencies of rs292001 and rs294183 between preeclamptic and normotensive women were observed. Likewise, there were no significant differences in allelic and genotype frequencies between HIV infected normotensive vs HIV infected preeclampsia and HIV uninfected normotensive vs HIV uninfected preeclampsia for both SNPs. However, the odds ratio of preeclamptic women having the GA genotype was 1:2.
Conclusion:
We demonstrate that SNPs of the C1q gene (rs292001 and rs294183) are not associated with the pathogenesis of PE development in women of African ancestry. The role ofC1qrs292001 heterozygous GA is highlighted (with and without HIV infection) may affect susceptibility to PE development. Notably, this dysregulation may affect C1q translation and protein output thus influencing the downstream role of the complement system and functional immunology in HIV infection comorbid with PE.
Related Concept Videos
01:05Single Nucleotide Polymorphisms-SNPs
02:26Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...