Yu-Jun Chen1, Julia Meyer2, Jennifer A Wambach2, Kelcey DePass2, Daniel J Wegner2, Xin Fan3, Qun-Yuan Zhang4, Heins Hillary2, F Sessions Cole2, Aaron Hamvas5,6. 1. Neonatology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China. 2. Division of Newborn Medicine, Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, USA. 3. Guangxi Maternal and Child Health Hospital, Nanning, China. 4. Department of Genetics, Washington University School of Medicine, St. Louis, USA. 5. Division of Newborn Medicine, Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, USA. ahamvas@luriechildrens.org. 6. Division of Neonatology, Ann and Robert H. Lurie Children's Hospital, 225 E. Chicago Ave, Box #45, Chicago, IL, 60611, USA. ahamvas@luriechildrens.org.
Abstract
BACKGROUND: To determine population-based prevalence and disease contribution of phosphatidylcholine synthetic pathway-associated gene variants in a native southern Chinese cohort. METHODS: We used bloodspots from 2010 that were obtained from the Guangxi Neonatal Screening Center in Nannning China and included the Han (n = 443) and Zhuang (n = 313) ethnic groups. We sequenced the exons of cholinephosphate cytidylyltransferase (PCYT1B) lysophospholipid acyltransferase 1 (LPCAT1), and cholinephosphotransferase (CHPT1) genes, and analyzed both rare and common exonic variants. RESULTS: We obtained five mutations (G199D, A299V, G434C, Y490C, L312S) with eight alleles in the three candidate genes. The collapsed minor allele frequency for candidate genes was not significantly different between the Han and Zhuang populations (0.0045 vs. 0.0064, respectively, P = 0.725). The combined Han and Zhuang pool collapsed carrier frequency of rare mutation allele was found to be 1.06%, which is much higher than previously reported for the Missouri population (0.1%). Further, we detected six exonic common variants (three in LPCAT1 and three in CHPT1), with three non-synonymous variants (F162S, F341L, M427K) among them. Two of the non-synonymous exonic variants (F341L, M427K) were not found in CHB; F341L was also not previously reported in exome sequencing project. CONCLUSIONS: The population-based frequency of mutations in the phosphatidylcholine synthesis pathway-associated genes PCYT1B LPCAT1, CHPT1 is low in southern Chinese newborns and there is no evidence of contribution to population-based disease burden of respiratory distress syndrome. As a population-based study of rare mutations and common variants, this work is valuable in directing future research.
BACKGROUND: To determine population-based prevalence and disease contribution of phosphatidylcholine synthetic pathway-associated gene variants in a native southern Chinese cohort. METHODS: We used bloodspots from 2010 that were obtained from the Guangxi Neonatal Screening Center in Nannning China and included the Han (n = 443) and Zhuang (n = 313) ethnic groups. We sequenced the exons of cholinephosphate cytidylyltransferase (PCYT1B) lysophospholipid acyltransferase 1 (LPCAT1), and cholinephosphotransferase (CHPT1) genes, and analyzed both rare and common exonic variants. RESULTS: We obtained five mutations (G199D, A299V, G434C, Y490C, L312S) with eight alleles in the three candidate genes. The collapsed minor allele frequency for candidate genes was not significantly different between the Han and Zhuang populations (0.0045 vs. 0.0064, respectively, P = 0.725). The combined Han and Zhuang pool collapsed carrier frequency of rare mutation allele was found to be 1.06%, which is much higher than previously reported for the Missouri population (0.1%). Further, we detected six exonic common variants (three in LPCAT1 and three in CHPT1), with three non-synonymous variants (F162S, F341L, M427K) among them. Two of the non-synonymous exonic variants (F341L, M427K) were not found in CHB; F341L was also not previously reported in exome sequencing project. CONCLUSIONS: The population-based frequency of mutations in the phosphatidylcholine synthesis pathway-associated genes PCYT1BLPCAT1, CHPT1 is low in southern Chinese newborns and there is no evidence of contribution to population-based disease burden of respiratory distress syndrome. As a population-based study of rare mutations and common variants, this work is valuable in directing future research.
Entities:
Keywords:
Genetic epidemiology; Human population genetics; Neonatal respiratory distress syndrome; Pulmonary surfactant
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