PTX3 genetic variation and dizygotic twinning in the Gambia: could pleiotropy with innate immunity explain common dizygotic twinning in Africa? | LitMetric
MRC Laboratories, Fajara, The Gambia, West Africa.
Published: November 2012
AI Article Synopsis
Article Abstract
Dizygotic (DZ) twinning has a genetic component and is common among sub-Saharan Africans; in The Gambia its frequency is up to 3% of live births. Variation in PTX3, encoding Pentraxin 3, a soluble pattern recognition receptor that plays an important role both in innate immunity and in female fertility, has been associated with resistance to Mycobacterium tuberculosis pulmonary disease and to Pseudomonas aeruginosa infection in cystic fibrosis patients. We tested whether PTX3 variants in Gambian women associate with DZ twinning, by genotyping five PTX3 single nucleotide polymorphisms (SNPs) in 130 sister pairs (96 full sibs and 34 half sibs) who had DZ twins. Two, three and five SNP haplotypes differed in frequency between twinning mothers and those without a history of twinning (from P = 0.006 to 3.03e-06 for two SNP and three SNP haplotypes, respectively). Twinning mothers and West African tuberculosis-controls from a previous study shared several frequent haplotypes. Most importantly, our data are consistent with an independently reported association of PTX3 and female fertility in a sample from Ghana. Taken together, these results indicate that selective pressure on PTX3 variants that affect the innate immune response to infectious agents, could also produce the observed high incidence of DZ twinning in Gambians.
Monozygotic (MZ) and dizygotic (DZ) twins are studied to understand genetic and environmental influences on complex traits, however the mechanisms behind twinning are not completely understood. (Epi)genomic studies identified SNPs associated with DZ twinning and DNA methylation sites with MZ twinning. To find molecular biomarkers of twinning, we compared transcriptomics and metabolomics data from MZ and DZ twins.
Induction of parthenogenesis (embryo formation from unfertilized egg cells) by embryogenic transcription factors is associated with twin formation at high frequencies, and involves two distinct mechanisms. Synthetic apomixis has been achieved through the induction of parthenogenesis by ectopic expression of the Baby Boom family of transcription factors. An associated phenomenon from this process is the formation of polyembryony including twin progeny at high frequencies, but the underlying mechanisms have not been explored.
Background: Monozygotic (MZ) twins are believed to arise from the fission of a single fertilized embryo at different stages. Monochorionic MZ twins, who share one chorion, originate from the splitting of the inner cell mass (ICM) within a single blastocyst. In the classic model for dichorionic MZ twins, the embryo splits before compaction, developing into two blastocysts.
While most dizygotic twins have a dichorionic placenta, rare cases of dizygotic twins with a monochorionic placenta have been reported. The monochorionic placenta in dizygotic twins allows in utero exchange of embryonic cells, resulting in chimerism in the twins. In practice, this chimerism is incidentally identified in mixed ABO blood types or in the presence of cells with a discordant sex chromosome.
A study examined fertility traits and family histories of dizygotic (DZ) twins among 972 Nigerian mothers of DZ twins and 525 controls, revealing significant genetic influences on twinning in the Nigerian population.
The research found that mothers of DZ twins (MoDZT) had an average of 4.0 pairs of twins in their relatives, significantly higher than the 0.5 pairs found in the control group, who also rarely had twins in their families.
MoDZT also had earlier childbirth ages and higher numbers of children compared to controls, suggesting enhanced fertility; furthermore, mothers with multiple sets of twins had even more twins in their families and had their first twins at a younger age, indicating a potential genetic predis
