title: Exome-wide association study identifies genetic polymorphisms of C12orf51, MYL2, and ALDH2 associated with blood lead levels in the general Korean population.
abstract: Lead (Pb) is a ubiquitous toxic metal present in the environment that poses adverse health effects to humans. Inter-individual variation in blood Pb levels is affected by various factors, including genetic makeup. However, limited data are available on the association between genetic variation and blood Pb levels. The purpose of this study was to identify the genetic markers associated with blood Pb levels in the Korean population.
  
  
  
  The study subjects consisted of 1,483 healthy adults with no history of occupational exposure to Pb. We measured blood Pb levels and calculated probable daily intake of Pb according to dietary data collected using 24-hour recall. We conducted exome-wide association screening using Illumina Human Exome-12v1.2 platform (n = 500) and a replication analysis using VeraCode Goldengate assay (n = 1,483).
  
  
  
  Among the 244,770 single nucleotide polymorphisms (SNPs) tested, 12 SNPs associated with blood Pb level were identified, with suggestive significance level (P < 1 × 10-4). In the Goldengate assay for replication, three SNPs (C12orf51 rs11066280, MYL2 rs12229654, and ALDH2 rs671) were associated with statistically suggestively significant differences in blood Pb levels. When stratified by drinking status, a potential association of C12orf51 rs11066280, MYL2 rs12229654, and ALDH2 rs671 with blood Pb level was observed only in drinkers. A marginally significant gene-environment interaction between ALDH2 rs671 and alcohol consumption was observed in relation to blood Pb levels. The effects of the three suggestively significant SNPs on blood Pb levels was dependent on daily calcium intake amounts.
  
  
  
  This exome-wide association study indicated that C12orf51 rs11066280, MYL2 rs12229654, and ALDH2 rs671 polymorphisms are linked to blood Pb levels in the Korean population. Our results suggest that these three SNPs are involved in the determination of Pb levels in Koreans via the regulation of alcohol drinking behavior, and that their negative effects may be compensated by appropriate calcium intake.
authors.affiliation: Department of Preventive Medicine, College of Medicine, Chungbuk National University, 1 Chungdae-Ro, Seowon-Gu, Cheongju, Chungbuk, 28644, Korea.
authors.forename: Sang-Yong
authors.initials: SY
authors.lastname: Eom
authors.affiliation: Food Risk Analysis Division, National Institute of Food and Drug Safety Evaluation, 187 Osongsaengmyeong 2-Ro, Heungdeok-Gu, Cheongju, 28159, Korea.
authors.forename: Myung Sil
authors.initials: MS
authors.lastname: Hwang
authors.affiliation: Department of Preventive Medicine, Dankook University College of Medicine, 119 Dandae-Ro, Dongnam-Gu, Cheonan, Chungnam, 31116, Korea.
authors.forename: Ji-Ae
authors.initials: JA
authors.lastname: Lim
authors.affiliation: Department of Preventive Medicine, Chung-Ang University College of Medicine, 84 Heukseok-Ro, Dongjak-Gu, Seoul, 06974, Korea.
authors.forename: Byung-Sun
authors.initials: BS
authors.lastname: Choi
authors.affiliation: Department of Preventive Medicine, Dankook University College of Medicine, 119 Dandae-Ro, Dongnam-Gu, Cheonan, Chungnam, 31116, Korea.
authors.forename: Ho-Jang
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Department of Preventive Medicine, Chung-Ang University College of Medicine, 84 Heukseok-Ro, Dongjak-Gu, Seoul, 06974, Korea.
authors.forename: Jung-Duck
authors.initials: JD
authors.lastname: Park
authors.affiliation: Department of Preventive Medicine, College of Medicine, Chungbuk National University, 1 Chungdae-Ro, Seowon-Gu, Cheongju, Chungbuk, 28644, Korea. ydkim@chungbuk.ac.kr.
authors.forename: Yong-Dae
authors.initials: YD
authors.lastname: Kim
authors.affiliation: Department of Preventive Medicine, College of Medicine, Chungbuk National University, 1 Chungdae-Ro, Seowon-Gu, Cheongju, Chungbuk, 28644, Korea.
authors.forename: Heon
authors.initials: H
authors.lastname: Kim
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D024722:Cardiac Myosins / Q000235:genetics*; D004785:Environmental Pollutants / Q000097:blood*; D059472:Exome; D005260:Female; D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study; D006801:Humans; D007854:Lead / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018994:Myosin Light Chains / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012907:Smoking / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D004785:Environmental Pollutants; D018994:Myosin Light Chains; C107184:myosin light chain 2; D007854:Lead; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C000609470:HECTD4 protein, human; D044767:Ubiquitin-Protein Ligases; D024722:Cardiac Myosins
keywords: Aldehyde dehydrogenase 2; Blood lead level; Exome-wide association study; Single nucleotide polymorphism