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...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
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Nature Publishing Group
2015
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| Online Access: | http://hdl.handle.net/20.500.11937/20441 |
| _version_ | 1848750305854881792 |
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| author | Wadley, A. Hendry, L. Kamerman, P. Chew, C. Price, Patricia Cherry, C. Lombard, Z. |
| author_facet | Wadley, A. Hendry, L. Kamerman, P. Chew, C. Price, Patricia Cherry, C. Lombard, Z. |
| author_sort | Wadley, A. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| 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. |
| first_indexed | 2025-11-14T07:34:44Z |
| format | Journal Article |
| id | curtin-20.500.11937-20441 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:34:44Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-204412017-09-13T13:50:23Z Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans Wadley, A. Hendry, L. Kamerman, P. Chew, C. Price, Patricia Cherry, C. Lombard, Z. 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. 2015 Journal Article http://hdl.handle.net/20.500.11937/20441 10.1038/ejhg.2014.104 Nature Publishing Group unknown |
| spellingShingle | Wadley, A. Hendry, L. Kamerman, P. Chew, C. Price, Patricia Cherry, C. Lombard, Z. Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans |
| title | Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans |
| title_full | Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans |
| title_fullStr | Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans |
| title_full_unstemmed | Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans |
| title_short | Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans |
| title_sort | role of tnf block genetic variants in hiv-associated sensory neuropathy in black southern africans |
| url | http://hdl.handle.net/20.500.11937/20441 |