Primate-specific evolution of noncoding element insertion into <it>PLA2G4C </it>and human preterm birth

• Main Authors: Fellman Vineta (Author), Peltonen Leena (Author), Palotie Aarno (Author), Snegovskikh Victoria (Author), Norwitz Errol (Author), Kuczynski Edward (Author), Menon Ramkumar (Author), Puttonen Hilkka (Author), Hallman Mikko (Author), Haataja Ritva (Author), Morgan Thomas (Author), Doniger Scott (Author), Plunkett Jevon (Author), DeFranco Emily A (Author), Chaudhari Bimal P (Author), Oates John (Author), Boutaud Olivier (Author), McGregor Tracy L (Author), McElroy Jude J (Author), Teramo Kari (Author), Borecki Ingrid (Author), Fay Justin C (Author), Muglia Louis J (Author)
• Format: Book
• Published: BMC, 2010-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Background</p> <p>The onset of birth in humans, like other apes, differs from non-primate mammals in its endocrine physiology. We hypothesize that higher primate-specific gene evolution may lead to these differences and target genes involved in human preterm birth, an area of global health significance.</p> <p>Methods</p> <p>We performed a comparative genomics screen of highly conserved noncoding elements and identified <it>PLA2G4C</it>, a phospholipase A isoform involved in prostaglandin biosynthesis as human accelerated. To examine whether this gene demonstrating primate-specific evolution was associated with birth timing, we genotyped and analyzed 8 common single nucleotide polymorphisms (SNPs) in <it>PLA2G4C </it>in US Hispanic (n = 73 preterm, 292 control), US White (n = 147 preterm, 157 control) and US Black (n = 79 preterm, 166 control) mothers.</p> <p>Results</p> <p>Detailed structural and phylogenic analysis of <it>PLA2G4C </it>suggested a short genomic element within the gene duplicated from a paralogous highly conserved element on chromosome 1 specifically in primates. SNPs rs8110925 and rs2307276 in US Hispanics and rs11564620 in US Whites were significant after correcting for multiple tests (p < 0.006). Additionally, rs11564620 (Thr360Pro) was associated with increased metabolite levels of the prostaglandin thromboxane in healthy individuals (p = 0.02), suggesting this variant may affect <it>PLA2G4C </it>activity.</p> <p>Conclusions</p> <p>Our findings suggest that variation in <it>PLA2G4C </it>may influence preterm birth risk by increasing levels of prostaglandins, which are known to regulate labor.</p>

Item Description

10.1186/1755-8794-3-62
1755-8794