Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans

Wadley, Antonia L.; Hendry, Liesl M.; Kamerman, Peter R.; Chew, Constance Sn; Price, Patricia; Cherry, Catherine L.; Lombard, Zané

doi:10.1038/ejhg.2014.104

Cited by 19 publications

(18 citation statements)

References 60 publications

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“…In Asians, the minor alleles of rs1800629 and rs9281523 occur as part of the diabetogenic 8.1 AH [19,20], consistent with a role for the region in immunopathology. The minor allele of rs9281523 associated with risk of HIV-SN in Caucasian patients who developed a toxic neuropathy following exposure to stavudine [6], but showed no effect in our cross-sectional studies of Indonesian or South African patients treated with stavudine [5,16]. Here, we assess two cohorts with no exposure to stavudine.…”

Section: Introductionmentioning

confidence: 91%

“…Thirteen SNP previously linked with HIV-SN either independently or within haplotypes were selected from across the TNF-block for genotyping in these cohorts (Table 2) [6,15,16]. In the Indonesian cohort, the minor alleles of rs9281523 (DDX39B/BAT1(intron10)) and rs1800629 (TNF-308) were more common in patients with HIV-SN.…”

Section: Two Alleles Associated With Hiv-sn In Indonesians But Not Afmentioning

confidence: 99%

“…The gene encoding TNF (TNF) lies in the central MHC in a defined region of high linkage disequilibrium (LD; the TNF-block), which contains several potentially pro-inflammatory genes (TNF, LTB, LTA, NCR3, LST1, NFKBIL1, ATP6V1G2, BAT1 (alternatively DDX39B) and MCCD1) [14]. Carriage of the minor allele at TNF-1031 (rs1799964) associated with increased risk of HIV-SN in Caucasians, Chinese and Malays who had received stavudine [5,6,15], but not in South Africans [16]. We characterized TNF-block haplotypes in multiple ethnicities and showed that the haplotype containing the minor allele of TNF-1031 in Asians and Caucasians was not present in Africans [14,16].…”

Section: Introductionmentioning

confidence: 99%

“…Carriage of the minor allele at TNF-1031 (rs1799964) associated with increased risk of HIV-SN in Caucasians, Chinese and Malays who had received stavudine [5,6,15], but not in South Africans [16]. We characterized TNF-block haplotypes in multiple ethnicities and showed that the haplotype containing the minor allele of TNF-1031 in Asians and Caucasians was not present in Africans [14,16]. This implicates an allele carried in linkage with TNF-1031 in its associations with HIV-SN.…”

Section: Introductionmentioning

confidence: 99%

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TNF-Block Genotypes Influence Susceptibility to HIV-Associated Sensory Neuropathy in Indonesians and South Africans

Gaff

Octaviana

Pillay

et al. 2020

IJMS

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HIV-associated sensory neuropathy (HIV-SN) is a disabling complication of HIV disease and antiretroviral therapies (ART). Since stavudine was removed from recommended treatment schedules, the prevalence of HIV-SN has declined and associated risk factors have changed. With stavudine, rs1799964*C (TNF-1031) associated with HIV-SN in Caucasians and Indonesians but not in South Africans. Here, we investigate associations between HIV-SN and rs1799964*C and 12 other polymorphisms spanning TNF and seven neighboring genes (the TNF-block) in Indonesians (n = 202; 34/168 cases) and South Africans (n = 75; 29/75 cases) treated without stavudine. Haplotypes were derived using fastPHASE and haplotype networks built with PopART. There were no associations with rs1799964*C in either population. However, rs9281523*C in intron 10 of BAT1 (alternatively DDX39B) independently associated with HIV-SN in Indonesians after correcting for lower CD4 T-cell counts and >500 copies of HIV RNA/mL (model p = 0.0011, Pseudo R 2 = 0.09). rs4947324*T (between NFKBIL1 and LTA) independently associated with reduced risk of HIV-SN and shared haplotype 1 (containing no minor alleles) associated with increased risk of HIV-SN after correcting for greater body weight, a history of tuberculosis and nadir CD4 T-cell counts (model: p = 0.0003, Pseudo R 2 = 0.22). These results confirm TNF-block genotypes influence susceptibility of HIV-SN. However, critical genotypes differ between ethnicities and with stavudine use.

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Section: Introductionmentioning

confidence: 91%

Section: Two Alleles Associated With Hiv-sn In Indonesians But Not Afmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

TNF-Block Genotypes Influence Susceptibility to HIV-Associated Sensory Neuropathy in Indonesians and South Africans

Gaff

Octaviana

Pillay

et al. 2020

IJMS

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“…Associations of HIV-associated sensory neuropathy including IL4 polymorphism [129], KCNS1 [130] and TNF block gene variants [131, 132] have been reported in South African cohorts while TP53 mutations detected in primary glioblastoma [133] and loss of heterogeneity and NF2 mutation in meningiomas [134] have been described in Morocco and South Africa respectively.…”

Section: Perspectives On What Is Knownmentioning

confidence: 99%

Neurogenomics in Africa: Perspectives, progress, possibilities and priorities

Akinyemi

Owolabi

Oyeniyi

et al. 2016

Journal of the Neurological Sciences

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The understanding of the genetic basis of neurological disorders has grown rapidly in the last two decades. Despite the genomic heterogeneity within African populations, large-scale candidate gene or linkage and exome studies are lacking. However, current knowledge on neurogenetics in African populations is limited and geographically very uneven. Isolated reports indicate the existence of autosomal dominant or recessive conditions incorporating cerebrovascular, movement, neuromuscular, seizure and motor neuron disorders in Africans. In addition, few African families with neurodegenerative disorders associated with dementia have been characterized in North, West and South Africa. The current insurgency in genomic research triggered by among others the Human Health and Heredity (H3) Africa Initiative indicates that there are unique opportunities to advance our knowledge and understanding of the influence of genomic variation on the pattern, presentations and prognosis of neurological disorders in Africa. These have enormous potential to unmask novel genes and molecular pathways germane to the neurobiology of brain disorders. It would facilitate the development of novel diagnostics, preventative and targeted treatments in the new paradigm of precision medicine. Nevertheless, it is crucial to strike a balance between effective traditional public health strategies and personalized genome based care. The translational barriers can be overcome through robust stakeholder engagement and sustainable multilevel, multigenerational and multidisciplinary capacity building and infrastructural development for genomic medicine in Africa.

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Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients

et al. 2016

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HIV-associated sensory neuropathy (HIV-SN) is the most common neurological condition associated with HIV. HIV-SN has characteristics of an inflammatory pathology caused by the virus itself and/or by antiretroviral treatment (ART). Here, we assess the impact of single-nucleotide polymorphisms (SNPs) in a cluster of three genes that affect inflammation and neuronal repair: P2X7R, P2X4R and CAMKK2. HIV-SN status was assessed using the Brief Peripheral Neuropathy Screening tool, with SN defined by bilateral symptoms and signs. Forty-five SNPs in P2X7R, P2X4R and CAMKK2 were genotyped using TaqMan fluorescent probes, in DNA samples from 153 HIV(+) black Southern African patients exposed to stavudine. Haplotypes were derived using the fastPHASE algorithm, and SNP genotypes and haplotypes associated with HIV-SN were identified. Optimal logistic regression models included demographics (age and height), with SNPs (model p < 0.0001; R (2) = 0.19) or haplotypes (model p < 0.0001; R (2) = 0.18, n = 137 excluding patients carrying CAMKK2 haplotypes perfectly associated with SN). Overall, CAMKK2 exhibited the strongest associations with HIV-SN, with two SNPs and six haplotypes predicting SN status in black Southern Africans. This gene warrants further study.

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Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans

Cited by 19 publications

References 60 publications

TNF-Block Genotypes Influence Susceptibility to HIV-Associated Sensory Neuropathy in Indonesians and South Africans

TNF-Block Genotypes Influence Susceptibility to HIV-Associated Sensory Neuropathy in Indonesians and South Africans

Neurogenomics in Africa: Perspectives, progress, possibilities and priorities

Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients

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