δ-Aminolevulinic Acid Dehydratase Genotype and Lead Toxicity: A HuGE Review
The ALAD gene (chromosome 9q34) codes for δ-aminolevulinic acid dehydratase (ALAD) (E.C. 4.2.1.24). ALAD catalyzes the second step of heme synthesis and is polymorphic. The ALAD G177C polymorphism yields two codominant alleles, ALAD-1 and ALAD-2, and it has been implicated in susceptibility to lead...
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| Veröffentlicht in: | American journal of epidemiology 2001-07, Vol.154 (1), p.1-13 |
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| creator | Kelada, Samir N. Shelton, Erin Kaufmann, Rachel B. Khoury, Muin J. |
| description | The ALAD gene (chromosome 9q34) codes for δ-aminolevulinic acid dehydratase (ALAD) (E.C. 4.2.1.24). ALAD catalyzes the second step of heme synthesis and is polymorphic. The ALAD G177C polymorphism yields two codominant alleles, ALAD-1 and ALAD-2, and it has been implicated in susceptibility to lead toxicity. Genotype frequencies vary by geography and race. The rarer ALAD-2 allele has been associated with high blood lead levels and has been thought to increase the risk of lead toxicity by generating a protein that binds lead more tightly than the ALAD-1 protein. Other evidence suggests that ALAD-2 may confer resistance to the harmful effects of lead by sequestering lead, making it unavailable for pathophysiologic participation. Recent studies have shown that individuals who are homozygous for the ALAD-1 allele have higher cortical bone lead levels; this implies that they may have a greater body lead burden and may be at higher risk of the long-term effects of lead. Individuals exposed to lead in occupational settings have been the most frequent subjects of study. Genotype selection bias may limit inferences from these studies. No firm evidence exists for an association between ALAD genotype and susceptibility to lead toxicity at background exposure levels; therefore, population testing for the ALAD polymorphism is not justified. |
| doi_str_mv | 10.1093/aje/154.1.1 |
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ALAD catalyzes the second step of heme synthesis and is polymorphic. The ALAD G177C polymorphism yields two codominant alleles, ALAD-1 and ALAD-2, and it has been implicated in susceptibility to lead toxicity. Genotype frequencies vary by geography and race. The rarer ALAD-2 allele has been associated with high blood lead levels and has been thought to increase the risk of lead toxicity by generating a protein that binds lead more tightly than the ALAD-1 protein. Other evidence suggests that ALAD-2 may confer resistance to the harmful effects of lead by sequestering lead, making it unavailable for pathophysiologic participation. Recent studies have shown that individuals who are homozygous for the ALAD-1 allele have higher cortical bone lead levels; this implies that they may have a greater body lead burden and may be at higher risk of the long-term effects of lead. Individuals exposed to lead in occupational settings have been the most frequent subjects of study. Genotype selection bias may limit inferences from these studies. No firm evidence exists for an association between ALAD genotype and susceptibility to lead toxicity at background exposure levels; therefore, population testing for the ALAD polymorphism is not justified.</description><identifier>ISSN: 0002-9262</identifier><identifier>EISSN: 1476-6256</identifier><identifier>EISSN: 0002-9262</identifier><identifier>DOI: 10.1093/aje/154.1.1</identifier><identifier>PMID: 11427399</identifier><identifier>CODEN: AJEPAS</identifier><language>eng</language><publisher>Cary, NC: Oxford University Press</publisher><subject>ALAD ; aminolevulinic acid ; aminolevulinic acid dehydratase ; Biological and medical sciences ; Chemical and industrial products toxicology. Toxic occupational diseases ; dimercaptosuccinic acid ; DMSA ; epidemiology ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genome, Human ; Genotype ; hereditary hemochromatosis gene ; HFE ; Humans ; lead ; lead poisoning ; Lead Poisoning - enzymology ; Lead Poisoning - epidemiology ; Lead Poisoning - genetics ; Medical sciences ; Metals and various inorganic compounds ; Molecular Structure ; National Health and Nutrition Examination Survey ; NHANES ; Polymorphism, Genetic ; porphobilinogen synthase ; Porphobilinogen Synthase - genetics ; Porphobilinogen Synthase - metabolism ; standard deviation ; Toxicology ; VDR ; vitamin D receptor</subject><ispartof>American journal of epidemiology, 2001-07, Vol.154 (1), p.1-13</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c420t-3fe5ee8f53062d8a9cf46832e4f7ba7c3712a1b81bfdcc14711821145a7094683</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1054542$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11427399$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kelada, Samir N.</creatorcontrib><creatorcontrib>Shelton, Erin</creatorcontrib><creatorcontrib>Kaufmann, Rachel B.</creatorcontrib><creatorcontrib>Khoury, Muin J.</creatorcontrib><title>δ-Aminolevulinic Acid Dehydratase Genotype and Lead Toxicity: A HuGE Review</title><title>American journal of epidemiology</title><addtitle>Am. J. Epidemiol</addtitle><description>The ALAD gene (chromosome 9q34) codes for δ-aminolevulinic acid dehydratase (ALAD) (E.C. 4.2.1.24). ALAD catalyzes the second step of heme synthesis and is polymorphic. The ALAD G177C polymorphism yields two codominant alleles, ALAD-1 and ALAD-2, and it has been implicated in susceptibility to lead toxicity. Genotype frequencies vary by geography and race. The rarer ALAD-2 allele has been associated with high blood lead levels and has been thought to increase the risk of lead toxicity by generating a protein that binds lead more tightly than the ALAD-1 protein. Other evidence suggests that ALAD-2 may confer resistance to the harmful effects of lead by sequestering lead, making it unavailable for pathophysiologic participation. Recent studies have shown that individuals who are homozygous for the ALAD-1 allele have higher cortical bone lead levels; this implies that they may have a greater body lead burden and may be at higher risk of the long-term effects of lead. Individuals exposed to lead in occupational settings have been the most frequent subjects of study. Genotype selection bias may limit inferences from these studies. No firm evidence exists for an association between ALAD genotype and susceptibility to lead toxicity at background exposure levels; therefore, population testing for the ALAD polymorphism is not justified.</description><subject>ALAD</subject><subject>aminolevulinic acid</subject><subject>aminolevulinic acid dehydratase</subject><subject>Biological and medical sciences</subject><subject>Chemical and industrial products toxicology. Toxic occupational diseases</subject><subject>dimercaptosuccinic acid</subject><subject>DMSA</subject><subject>epidemiology</subject><subject>Gene Frequency</subject><subject>Genetic Predisposition to Disease</subject><subject>genetics</subject><subject>Genome, Human</subject><subject>Genotype</subject><subject>hereditary hemochromatosis gene</subject><subject>HFE</subject><subject>Humans</subject><subject>lead</subject><subject>lead poisoning</subject><subject>Lead Poisoning - enzymology</subject><subject>Lead Poisoning - epidemiology</subject><subject>Lead Poisoning - genetics</subject><subject>Medical sciences</subject><subject>Metals and various inorganic compounds</subject><subject>Molecular Structure</subject><subject>National Health and Nutrition Examination Survey</subject><subject>NHANES</subject><subject>Polymorphism, Genetic</subject><subject>porphobilinogen synthase</subject><subject>Porphobilinogen Synthase - genetics</subject><subject>Porphobilinogen Synthase - metabolism</subject><subject>standard deviation</subject><subject>Toxicology</subject><subject>VDR</subject><subject>vitamin D receptor</subject><issn>0002-9262</issn><issn>1476-6256</issn><issn>0002-9262</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpN0MFKw0AQBuBFFK3Vk3fZg3iR1J3NbpL1VqpthYBQKoiXZbuZ4Gqa1Gyi9r18Dp_JSIt6msN8_Mz8hJwAGwBT4aV5xkuQYgAD2CE9EHEURFxGu6THGOOB4hE_IIfePzMGoCTbJwcAgsehUj2Sfn0Gw6UrqwLf2sKVztKhdRm9xqd1VpvGeKQTLKtmvUJqyoymaDI6rz6cdc36ig7ptJ3c0Bm-OXw_Inu5KTweb2ef3I9v5qNpkN5NbkfDNLCCsyYIc5SISS5DFvEsMcrmIkpCjiKPFya2YQzcwCKBRZ5Z2z0EkPDuZGlipn5kn5xvcld19dqib_TSeYtFYUqsWq8hEYkSIDt4sYG2rryvMder2i1NvdbA9E95uitPd-Vp0NDp021su1hi9me3bXXgbAuMt6bIa1Na5_9lSiEF71iwYc43-PG7NvWLjuIwlnr68KhnKZ_MlBrrefgNzSyFNw</recordid><startdate>20010701</startdate><enddate>20010701</enddate><creator>Kelada, Samir N.</creator><creator>Shelton, Erin</creator><creator>Kaufmann, Rachel B.</creator><creator>Khoury, Muin J.</creator><general>Oxford University Press</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20010701</creationdate><title>δ-Aminolevulinic Acid Dehydratase Genotype and Lead Toxicity: A HuGE Review</title><author>Kelada, Samir N. ; Shelton, Erin ; Kaufmann, Rachel B. ; Khoury, Muin J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c420t-3fe5ee8f53062d8a9cf46832e4f7ba7c3712a1b81bfdcc14711821145a7094683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>ALAD</topic><topic>aminolevulinic acid</topic><topic>aminolevulinic acid dehydratase</topic><topic>Biological and medical sciences</topic><topic>Chemical and industrial products toxicology. Toxic occupational diseases</topic><topic>dimercaptosuccinic acid</topic><topic>DMSA</topic><topic>epidemiology</topic><topic>Gene Frequency</topic><topic>Genetic Predisposition to Disease</topic><topic>genetics</topic><topic>Genome, Human</topic><topic>Genotype</topic><topic>hereditary hemochromatosis gene</topic><topic>HFE</topic><topic>Humans</topic><topic>lead</topic><topic>lead poisoning</topic><topic>Lead Poisoning - enzymology</topic><topic>Lead Poisoning - epidemiology</topic><topic>Lead Poisoning - genetics</topic><topic>Medical sciences</topic><topic>Metals and various inorganic compounds</topic><topic>Molecular Structure</topic><topic>National Health and Nutrition Examination Survey</topic><topic>NHANES</topic><topic>Polymorphism, Genetic</topic><topic>porphobilinogen synthase</topic><topic>Porphobilinogen Synthase - genetics</topic><topic>Porphobilinogen Synthase - metabolism</topic><topic>standard deviation</topic><topic>Toxicology</topic><topic>VDR</topic><topic>vitamin D receptor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kelada, Samir N.</creatorcontrib><creatorcontrib>Shelton, Erin</creatorcontrib><creatorcontrib>Kaufmann, Rachel B.</creatorcontrib><creatorcontrib>Khoury, Muin J.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>American journal of epidemiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kelada, Samir N.</au><au>Shelton, Erin</au><au>Kaufmann, Rachel B.</au><au>Khoury, Muin J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>δ-Aminolevulinic Acid Dehydratase Genotype and Lead Toxicity: A HuGE Review</atitle><jtitle>American journal of epidemiology</jtitle><addtitle>Am. J. Epidemiol</addtitle><date>2001-07-01</date><risdate>2001</risdate><volume>154</volume><issue>1</issue><spage>1</spage><epage>13</epage><pages>1-13</pages><issn>0002-9262</issn><eissn>1476-6256</eissn><eissn>0002-9262</eissn><coden>AJEPAS</coden><abstract>The ALAD gene (chromosome 9q34) codes for δ-aminolevulinic acid dehydratase (ALAD) (E.C. 4.2.1.24). ALAD catalyzes the second step of heme synthesis and is polymorphic. The ALAD G177C polymorphism yields two codominant alleles, ALAD-1 and ALAD-2, and it has been implicated in susceptibility to lead toxicity. Genotype frequencies vary by geography and race. The rarer ALAD-2 allele has been associated with high blood lead levels and has been thought to increase the risk of lead toxicity by generating a protein that binds lead more tightly than the ALAD-1 protein. Other evidence suggests that ALAD-2 may confer resistance to the harmful effects of lead by sequestering lead, making it unavailable for pathophysiologic participation. Recent studies have shown that individuals who are homozygous for the ALAD-1 allele have higher cortical bone lead levels; this implies that they may have a greater body lead burden and may be at higher risk of the long-term effects of lead. Individuals exposed to lead in occupational settings have been the most frequent subjects of study. Genotype selection bias may limit inferences from these studies. No firm evidence exists for an association between ALAD genotype and susceptibility to lead toxicity at background exposure levels; therefore, population testing for the ALAD polymorphism is not justified.</abstract><cop>Cary, NC</cop><pub>Oxford University Press</pub><pmid>11427399</pmid><doi>10.1093/aje/154.1.1</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | ALAD aminolevulinic acid aminolevulinic acid dehydratase Biological and medical sciences Chemical and industrial products toxicology. Toxic occupational diseases dimercaptosuccinic acid DMSA epidemiology Gene Frequency Genetic Predisposition to Disease genetics Genome, Human Genotype hereditary hemochromatosis gene HFE Humans lead lead poisoning Lead Poisoning - enzymology Lead Poisoning - epidemiology Lead Poisoning - genetics Medical sciences Metals and various inorganic compounds Molecular Structure National Health and Nutrition Examination Survey NHANES Polymorphism, Genetic porphobilinogen synthase Porphobilinogen Synthase - genetics Porphobilinogen Synthase - metabolism standard deviation Toxicology VDR vitamin D receptor |
| title | δ-Aminolevulinic Acid Dehydratase Genotype and Lead Toxicity: A HuGE Review |
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