Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans
HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection. The TNF block is a region within the central MHC that contains many immunoregulatory genes. Polymorphisms and haplotypes of the TNF block have been associated with increased risk of HIV-SN in Asians an...
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| Veröffentlicht in: | European journal of human genetics : EJHG 2015-03, Vol.23 (3), p.363-368 |
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| creator | Wadley, Antonia L Hendry, Liesl M Kamerman, Peter R Chew, Constance S N Price, Patricia Cherry, Catherine L Lombard, Zané |
| description | HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection. The TNF block is a region within the central MHC that contains many immunoregulatory genes. Polymorphisms and haplotypes of the TNF block have been associated with increased risk of HIV-SN in Asians and whites. Here we investigated genetic associations with HIV-SN in 342 black Southern Africans (190 cases and 152 neuropathy-free controls) using single nucleotide polymorphisms (SNPs) spanning the TNF block and a set of haplotypes defined by 31 SNPs in Asian and white populations (denoted FVa). We included population-appropriate tagSNPs derived from an African population (Yoruban, YRI, HapMap) and derived extended haplotypes comprising 61 SNPs (denoted FVa_ext b). We found no association between HIV-SN and carriage of two SNPs (TNF-1031/rs1799964*C and BAT1 (intron10)/rs9281523*C) associated with HIV-SN in whites and Asians. Additionally, a haplotype containing TNF-1031/rs1799964*C associated with increased risk of HIV-SN in Asians, but was not present in this African population. However, alleles of seven SNPs associated with reduced risk of HIV-SN (corrected for age, height and multiple comparisons). These were rs11796*A, rs3130059*G, rs2071594*C, NFKBIL1-62/rs2071592*A, rs2071591*A, LTA+252/rs909253*G, rs1041981*C. One haplotype (FV18_ext1), not containing these alleles, was associated with increased risk of HIV-SN after correction for age, height and multiple comparisons. Our results confirm the involvement of genes in the TNF block in altering risk for HIV-SN, but genotypes critical in this African population differed from those affecting HIV-SN in whites and Asians. These differences support the need for genetic association studies in diverse populations. |
| doi_str_mv | 10.1038/ejhg.2014.104 |
| format | Article |
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The TNF block is a region within the central MHC that contains many immunoregulatory genes. Polymorphisms and haplotypes of the TNF block have been associated with increased risk of HIV-SN in Asians and whites. Here we investigated genetic associations with HIV-SN in 342 black Southern Africans (190 cases and 152 neuropathy-free controls) using single nucleotide polymorphisms (SNPs) spanning the TNF block and a set of haplotypes defined by 31 SNPs in Asian and white populations (denoted FVa). We included population-appropriate tagSNPs derived from an African population (Yoruban, YRI, HapMap) and derived extended haplotypes comprising 61 SNPs (denoted FVa_ext b). We found no association between HIV-SN and carriage of two SNPs (TNF-1031/rs1799964*C and BAT1 (intron10)/rs9281523*C) associated with HIV-SN in whites and Asians. Additionally, a haplotype containing TNF-1031/rs1799964*C associated with increased risk of HIV-SN in Asians, but was not present in this African population. However, alleles of seven SNPs associated with reduced risk of HIV-SN (corrected for age, height and multiple comparisons). These were rs11796*A, rs3130059*G, rs2071594*C, NFKBIL1-62/rs2071592*A, rs2071591*A, LTA+252/rs909253*G, rs1041981*C. One haplotype (FV18_ext1), not containing these alleles, was associated with increased risk of HIV-SN after correction for age, height and multiple comparisons. Our results confirm the involvement of genes in the TNF block in altering risk for HIV-SN, but genotypes critical in this African population differed from those affecting HIV-SN in whites and Asians. These differences support the need for genetic association studies in diverse populations.</description><identifier>ISSN: 1018-4813</identifier><identifier>EISSN: 1476-5438</identifier><identifier>DOI: 10.1038/ejhg.2014.104</identifier><identifier>PMID: 24896147</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Adult ; African Continental Ancestry Group ; Alleles ; Chromosomes ; Chromosomes, Human, Pair 6 ; Diabetes ; Female ; Genes ; Genetic diversity ; Genetic Loci ; Genetic variance ; Genetic Variation ; Genomics ; Haplotypes ; Health sciences ; Heart attacks ; HIV ; HIV Infections - complications ; Human immunodeficiency virus ; Humans ; Immunoregulation ; Laboratories ; Major histocompatibility complex ; Male ; Middle Aged ; Neuropathy ; Odds Ratio ; Pathogenesis ; Peripheral Nervous System Diseases - etiology ; Phenotype ; Physiology ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Population ; Population genetics ; Population studies ; Rheumatoid arthritis ; Single-nucleotide polymorphism ; Studies ; Tumor necrosis factor ; Tumor Necrosis Factor-alpha - genetics ; Tumor necrosis factor-TNF</subject><ispartof>European journal of human genetics : EJHG, 2015-03, Vol.23 (3), p.363-368</ispartof><rights>Copyright Nature Publishing Group Mar 2015</rights><rights>Copyright © 2015 Macmillan Publishers Limited 2015 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c518t-53553147aef6c9c43d5206e765383155a196276c541c79dbaee3597098274bd93</citedby><cites>FETCH-LOGICAL-c518t-53553147aef6c9c43d5206e765383155a196276c541c79dbaee3597098274bd93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326702/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326702/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24896147$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wadley, Antonia L</creatorcontrib><creatorcontrib>Hendry, Liesl M</creatorcontrib><creatorcontrib>Kamerman, Peter R</creatorcontrib><creatorcontrib>Chew, Constance S N</creatorcontrib><creatorcontrib>Price, Patricia</creatorcontrib><creatorcontrib>Cherry, Catherine L</creatorcontrib><creatorcontrib>Lombard, Zané</creatorcontrib><title>Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans</title><title>European journal of human genetics : EJHG</title><addtitle>Eur J Hum Genet</addtitle><description>HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection. The TNF block is a region within the central MHC that contains many immunoregulatory genes. Polymorphisms and haplotypes of the TNF block have been associated with increased risk of HIV-SN in Asians and whites. Here we investigated genetic associations with HIV-SN in 342 black Southern Africans (190 cases and 152 neuropathy-free controls) using single nucleotide polymorphisms (SNPs) spanning the TNF block and a set of haplotypes defined by 31 SNPs in Asian and white populations (denoted FVa). We included population-appropriate tagSNPs derived from an African population (Yoruban, YRI, HapMap) and derived extended haplotypes comprising 61 SNPs (denoted FVa_ext b). We found no association between HIV-SN and carriage of two SNPs (TNF-1031/rs1799964*C and BAT1 (intron10)/rs9281523*C) associated with HIV-SN in whites and Asians. Additionally, a haplotype containing TNF-1031/rs1799964*C associated with increased risk of HIV-SN in Asians, but was not present in this African population. However, alleles of seven SNPs associated with reduced risk of HIV-SN (corrected for age, height and multiple comparisons). These were rs11796*A, rs3130059*G, rs2071594*C, NFKBIL1-62/rs2071592*A, rs2071591*A, LTA+252/rs909253*G, rs1041981*C. One haplotype (FV18_ext1), not containing these alleles, was associated with increased risk of HIV-SN after correction for age, height and multiple comparisons. Our results confirm the involvement of genes in the TNF block in altering risk for HIV-SN, but genotypes critical in this African population differed from those affecting HIV-SN in whites and Asians. These differences support the need for genetic association studies in diverse populations.</description><subject>Adult</subject><subject>African Continental Ancestry Group</subject><subject>Alleles</subject><subject>Chromosomes</subject><subject>Chromosomes, Human, Pair 6</subject><subject>Diabetes</subject><subject>Female</subject><subject>Genes</subject><subject>Genetic diversity</subject><subject>Genetic Loci</subject><subject>Genetic variance</subject><subject>Genetic Variation</subject><subject>Genomics</subject><subject>Haplotypes</subject><subject>Health sciences</subject><subject>Heart attacks</subject><subject>HIV</subject><subject>HIV Infections - complications</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immunoregulation</subject><subject>Laboratories</subject><subject>Major histocompatibility complex</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neuropathy</subject><subject>Odds Ratio</subject><subject>Pathogenesis</subject><subject>Peripheral Nervous System Diseases - etiology</subject><subject>Phenotype</subject><subject>Physiology</subject><subject>Polymorphism, Genetic</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population</subject><subject>Population genetics</subject><subject>Population studies</subject><subject>Rheumatoid arthritis</subject><subject>Single-nucleotide polymorphism</subject><subject>Studies</subject><subject>Tumor necrosis factor</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Tumor necrosis factor-TNF</subject><issn>1018-4813</issn><issn>1476-5438</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkc1rFTEUxYMotlaXbiXgxs3UfCezEUppbaFYqG23IZO5816e85JnMlN4_70ZWou6cpUc7i-Hc3MQek_JMSXcfIbNenXMCBVVihfokAqtGim4eVnvhJpGGMoP0JtSNqRSWtPX6IAJ06oqDlF3k0bAacC3385xNyb_A68gwhQ8fnA5uDgVHCK-uLxvXCnJBzdBjwvEkvIeR5hz2rlpvV-gbnT1-fc0T2vIEZ8MOXgXy1v0anBjgXdP5xG6Oz-7Pb1orq6_Xp6eXDVeUjM1kkvJayYHg_KtF7yXjCjQSnLDqZSOtopp5aWgXrd95wC4bDVpDdOi61t-hL48-u7mbgu9hzhlN9pdDluX9za5YP-exLC2q_RgBWdKE1YNPj0Z5PRzhjLZbSgextFFSHOxVCnBiBaC_wcqJZOaS1PRj_-gmzTnWH9ioYQSuhUL1TxSPqdSMgzPuSmxS9F2KdouRVcpKv_hz2Wf6d_N8l-GFKM2</recordid><startdate>20150301</startdate><enddate>20150301</enddate><creator>Wadley, Antonia L</creator><creator>Hendry, Liesl M</creator><creator>Kamerman, Peter R</creator><creator>Chew, Constance S N</creator><creator>Price, Patricia</creator><creator>Cherry, Catherine L</creator><creator>Lombard, Zané</creator><general>Nature Publishing Group</general><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150301</creationdate><title>Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans</title><author>Wadley, Antonia L ; Hendry, Liesl M ; Kamerman, Peter R ; Chew, Constance S N ; Price, Patricia ; Cherry, Catherine L ; Lombard, Zané</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c518t-53553147aef6c9c43d5206e765383155a196276c541c79dbaee3597098274bd93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>African Continental Ancestry Group</topic><topic>Alleles</topic><topic>Chromosomes</topic><topic>Chromosomes, Human, Pair 6</topic><topic>Diabetes</topic><topic>Female</topic><topic>Genes</topic><topic>Genetic diversity</topic><topic>Genetic Loci</topic><topic>Genetic variance</topic><topic>Genetic Variation</topic><topic>Genomics</topic><topic>Haplotypes</topic><topic>Health sciences</topic><topic>Heart attacks</topic><topic>HIV</topic><topic>HIV Infections - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European journal of human genetics : EJHG</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wadley, Antonia L</au><au>Hendry, Liesl M</au><au>Kamerman, Peter R</au><au>Chew, Constance S N</au><au>Price, Patricia</au><au>Cherry, Catherine L</au><au>Lombard, Zané</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans</atitle><jtitle>European journal of human genetics : EJHG</jtitle><addtitle>Eur J Hum Genet</addtitle><date>2015-03-01</date><risdate>2015</risdate><volume>23</volume><issue>3</issue><spage>363</spage><epage>368</epage><pages>363-368</pages><issn>1018-4813</issn><eissn>1476-5438</eissn><abstract>HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection. The TNF block is a region within the central MHC that contains many immunoregulatory genes. Polymorphisms and haplotypes of the TNF block have been associated with increased risk of HIV-SN in Asians and whites. Here we investigated genetic associations with HIV-SN in 342 black Southern Africans (190 cases and 152 neuropathy-free controls) using single nucleotide polymorphisms (SNPs) spanning the TNF block and a set of haplotypes defined by 31 SNPs in Asian and white populations (denoted FVa). We included population-appropriate tagSNPs derived from an African population (Yoruban, YRI, HapMap) and derived extended haplotypes comprising 61 SNPs (denoted FVa_ext b). We found no association between HIV-SN and carriage of two SNPs (TNF-1031/rs1799964*C and BAT1 (intron10)/rs9281523*C) associated with HIV-SN in whites and Asians. Additionally, a haplotype containing TNF-1031/rs1799964*C associated with increased risk of HIV-SN in Asians, but was not present in this African population. However, alleles of seven SNPs associated with reduced risk of HIV-SN (corrected for age, height and multiple comparisons). These were rs11796*A, rs3130059*G, rs2071594*C, NFKBIL1-62/rs2071592*A, rs2071591*A, LTA+252/rs909253*G, rs1041981*C. One haplotype (FV18_ext1), not containing these alleles, was associated with increased risk of HIV-SN after correction for age, height and multiple comparisons. Our results confirm the involvement of genes in the TNF block in altering risk for HIV-SN, but genotypes critical in this African population differed from those affecting HIV-SN in whites and Asians. These differences support the need for genetic association studies in diverse populations.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>24896147</pmid><doi>10.1038/ejhg.2014.104</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult African Continental Ancestry Group Alleles Chromosomes Chromosomes, Human, Pair 6 Diabetes Female Genes Genetic diversity Genetic Loci Genetic variance Genetic Variation Genomics Haplotypes Health sciences Heart attacks HIV HIV Infections - complications Human immunodeficiency virus Humans Immunoregulation Laboratories Major histocompatibility complex Male Middle Aged Neuropathy Odds Ratio Pathogenesis Peripheral Nervous System Diseases - etiology Phenotype Physiology Polymorphism, Genetic Polymorphism, Single Nucleotide Population Population genetics Population studies Rheumatoid arthritis Single-nucleotide polymorphism Studies Tumor necrosis factor Tumor Necrosis Factor-alpha - genetics Tumor necrosis factor-TNF |
| title | Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans |
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