TY - JOUR
T1 - Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth
AU - Plunkett, Jevon
AU - Doniger, Scott
AU - Morgan, Thomas
AU - Haataja, Ritva
AU - Hallman, Mikko
AU - Puttonen, Hilkka
AU - Menon, Ramkumar
AU - Kuczynski, Edward
AU - Norwitz, Errol
AU - Snegovskikh, Victoria
AU - Palotie, Aarno
AU - Peltonen, Leena
AU - Fellman, Vineta
AU - DeFranco, Emily A.
AU - Chaudhari, Bimal P.
AU - Oates, John
AU - Boutaud, Olivier
AU - McGregor, Tracy L.
AU - McElroy, Jude J.
AU - Teramo, Kari
AU - Borecki, Ingrid
AU - Fay, Justin C.
AU - Muglia, Louis J.
PY - 2010
Y1 - 2010
N2 - Background: 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. Methods: We performed a comparative genomics screen of highly conserved noncoding elements and identified PLA2G4C, 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 PLA2G4C in US Hispanic (n = 73 preterm, 292 control), US White (n = 147 preterm, 157 control) and US Black (n = 79 preterm, 166 control) mothers. Results: Detailed structural and phylogenic analysis of PLA2G4C 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 PLA2G4C activity. Conclusions: Our findings suggest that variation in PLA2G4C may influence preterm birth risk by increasing levels of prostaglandins, which are known to regulate labor.
AB - Background: 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. Methods: We performed a comparative genomics screen of highly conserved noncoding elements and identified PLA2G4C, 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 PLA2G4C in US Hispanic (n = 73 preterm, 292 control), US White (n = 147 preterm, 157 control) and US Black (n = 79 preterm, 166 control) mothers. Results: Detailed structural and phylogenic analysis of PLA2G4C 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 PLA2G4C activity. Conclusions: Our findings suggest that variation in PLA2G4C may influence preterm birth risk by increasing levels of prostaglandins, which are known to regulate labor.
U2 - 10.1186/1755-8794-3-62
DO - 10.1186/1755-8794-3-62
M3 - Article
C2 - 21184677
SN - 1755-8794
VL - 3
JO - BMC Medical Genomics
JF - BMC Medical Genomics
ER -
