Role of TNF Block Genetic Variants in HIV-associated Sensory Neuropathy in Black Southern Africans

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2014 Jun 5

PMID 24896147

Citations 12

Authors

Antonia L Wadley

Liesl M Hendry

Peter R Kamerman

Constance S N Chew

Patricia Price

Catherine L Cherry

Zane Lombard

Affiliations

Soon will be listed here.

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.

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References

Santos M, Carmona-Fernandes D, Caetano-Lopes J, Perpetuo I, Vidal B, Capela S . TNF promoter -308 G>A and LTA 252 A>G polymorphisms in Portuguese patients with systemic lupus erythematosus. Rheumatol Int. 2011; 32(8):2239-44. DOI: 10.1007/s00296-011-1950-7. View

Martinez A, Fernandez-Arquero M, Pascual-Salcedo D, Conejero L, Alves H, Balsa A . Primary association of tumor necrosis factor-region genetic markers with susceptibility to rheumatoid arthritis. Arthritis Rheum. 2000; 43(6):1366-70. DOI: 10.1002/1529-0131(200006)43:6<1366::AID-ANR21>3.0.CO;2-S. View

Miller S, Dykes D, Polesky H . A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3):1215. PMC: 334765. DOI: 10.1093/nar/16.3.1215. View

Lane A, Soodyall H, Arndt S, Ratshikhopha M, Jonker E, Freeman C . Genetic substructure in South African Bantu-speakers: evidence from autosomal DNA and Y-chromosome studies. Am J Phys Anthropol. 2002; 119(2):175-85. DOI: 10.1002/ajpa.10097. View

Phillips T, Cherry C, Cox S, Marshall S, Rice A . Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled trials. PLoS One. 2011; 5(12):e14433. PMC: 3010990. DOI: 10.1371/journal.pone.0014433. View

Cherry C, Wesselingh S, Lal L, McArthur J . Evaluation of a clinical screening tool for HIV-associated sensory neuropathies. Neurology. 2005; 65(11):1778-81. DOI: 10.1212/01.wnl.0000187119.33075.41. View

Feng R, Li Y, Sun C . TNF 308 G/A polymorphism and type 1 diabetes: a meta-analysis. Diabetes Res Clin Pract. 2009; 85(1):e4-7. DOI: 10.1016/j.diabres.2009.04.026. View

Hussein Y, Mohamed R, Pasha H, El-Shahawy E, Alzahrani S . Association of tumor necrosis factor alpha and its receptor polymorphisms with rheumatoid arthritis in female patients. Cell Immunol. 2011; 271(1):192-6. DOI: 10.1016/j.cellimm.2011.06.023. View

Tan J, Temple S, Kee C, Waterer G, Tan C, Gut I . Characterisation of TNF block haplotypes affecting the production of TNF and LTA. Tissue Antigens. 2011; 77(2):100-6. DOI: 10.1111/j.1399-0039.2010.01582.x. View

10.

Stephens M, Scheet P . Accounting for decay of linkage disequilibrium in haplotype inference and missing-data imputation. Am J Hum Genet. 2005; 76(3):449-62. PMC: 1196397. DOI: 10.1086/428594. View

11.

Valente F, Tan C, Phipps M, Witt C, Kaur G, Gut I . TNF block haplotypes associated with conserved MHC haplotypes in European, Asian and Australian Aboriginal donors. Tissue Antigens. 2009; 74(1):57-61. DOI: 10.1111/j.1399-0039.2009.01258.x. View

12.

Browning S, Browning B . Haplotype phasing: existing methods and new developments. Nat Rev Genet. 2011; 12(10):703-14. PMC: 3217888. DOI: 10.1038/nrg3054. View

13.

Maritz J, Benatar M, Dave J, Harrison T, Badri M, Levitt N . HIV neuropathy in South Africans: frequency, characteristics, and risk factors. Muscle Nerve. 2010; 41(5):599-606. DOI: 10.1002/mus.21535. View

14.

Hahn K, Robinson B, Anderson C, Li W, Pardo C, Morgello S . Differential effects of HIV infected macrophages on dorsal root ganglia neurons and axons. Exp Neurol. 2008; 210(1):30-40. PMC: 2270478. DOI: 10.1016/j.expneurol.2007.06.015. View

15.

Bolstad A, Le Hellard S, Kristjansdottir G, Vasaitis L, Kvarnstrom M, Sjowall C . Association between genetic variants in the tumour necrosis factor/lymphotoxin α/lymphotoxin β locus and primary Sjogren's syndrome in Scandinavian samples. Ann Rheum Dis. 2012; 71(6):981-8. DOI: 10.1136/annrheumdis-2011-200446. View

16.

Anziska Y, Helzner E, Crystal H, Glesby M, Plankey M, Weber K . The relationship between race and HIV-distal sensory polyneuropathy in a large cohort of US women. J Neurol Sci. 2011; 315(1-2):129-32. PMC: 3299869. DOI: 10.1016/j.jns.2011.11.009. View

17.

Campbell M, Tishkoff S . African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping. Annu Rev Genomics Hum Genet. 2008; 9:403-33. PMC: 2953791. DOI: 10.1146/annurev.genom.9.081307.164258. View

18.

Ozaki K, Ohnishi Y, Iida A, Sekine A, Yamada R, Tsunoda T . Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction. Nat Genet. 2002; 32(4):650-4. DOI: 10.1038/ng1047. View

19.

Stephens M, Smith N, Donnelly P . A new statistical method for haplotype reconstruction from population data. Am J Hum Genet. 2001; 68(4):978-89. PMC: 1275651. DOI: 10.1086/319501. View

20.

Boodhoo A, Wong A, Williamson D, Voon D, Lee S, Allcock R . A promoter polymorphism in the central MHC gene, IKBL, influences the binding of transcription factors USF1 and E47 on disease-associated haplotypes. Gene Expr. 2004; 12(1):1-11. PMC: 6009106. DOI: 10.3727/000000004783992206. View