GC Subtyping and HIV Infection in a Spanish Population: No Evidence of an Association between GC Subtypes and AIDS

Alonso, Antonio; Montesino, M.; Iturralde, Marı́a; Vallejo, Gavidia; Sancho, Maribel Iglesias; Varela, J.M.; Sáiz, Alfredo García; Nájera, Rafael

doi:10.1159/000153900

Cited by 9 publications

(3 citation statements)

References 9 publications

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“…The lack of association of VDBP locus variants with progression is in accordance with previous studies (Alonso et al, 1990;Cleve et al, 1988) discarding the earlier described association of VDBP variability with susceptibility to HIV-1 infection and progression to AIDS (Eales et al, 1987). In addition, our findings also evidence the lack of VDBP locus interaction with the tested vitamin-D pathway genes in the context of HIV-1 infection.…”

Section: Discussionsupporting

confidence: 92%

“…Several studies revealed the association between CYP27B1 polymorphisms and immune related diseases, such as Hashimoto's thyroiditis, Graves' disease and type 1/2 diabetes (Lopez et al, 2004) and Addison's disease (Jennings et al, 2005). VDBP polymorphisms have been associated with HIV-1 infection (Eales et al, 1987) but these findings have not been replicated (Alonso et al, 1990;Cleve et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

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Vitamin-D pathway genes and HIV-1 disease progression in injection drug users

Laplana

Sánchez‐de‐la‐Torre

Puig

et al. 2014

Gene

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Vitamin-D has pleiotropic effects on calcium and bone metabolism, cellular growth control, cell differentiation and modulation of both innate and acquired immune response. Previous studies revealed the association of vitamin-D receptor gene (VDR) polymorphism with infection diseases including HIV-1 infection. To assess for association between polymorphisms of vitamin-D pathway genes CYP27B1, vitamin-D binding protein (VDBP) and VDR with HIV-1 infection, disease progression to acquired immunodeficiency syndrome (AIDS) was analysed according to CDC93 criteria in a cohort of 185 HIV-1 seroprevalent patients belonging to the injection drug users. Genotype data was obtained from rs10877012, rs3782130 and rs4646536 markers at CYP27B1 locus; rs7041 and rs4588 at VDBP locus; and rs11568820, rs4516035, rs2228570, rs1544410 and rs17878969 at VDR locus. Distribution of genotypes between patients grouped by outcome was compared by contingency table analysis. Marker-marker interaction was assessed by a MDR analysis. Assuming an additive model for VDR markers, a Kaplan-Meier survival analysis was employed to evaluate association with disease progression. Among vitamin-D pathway genes, VDR locus reveals specific 5'UTR and 3'UTR diplotype combinations associated with both, slower and faster progression to AIDS. Marker-marker interaction analysis indicates a strong interaction between VDR markers and a redundant effect for CYP27B1 markers. According to our results, VDR locus association follows an additive model in which increased genetic risk score for the VDR is directly correlated with AIDS progression rates. Our data supports a role of vitamin-D pathway gene variability on HIV-1 disease progression.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Vitamin-D pathway genes and HIV-1 disease progression in injection drug users

Laplana

Sánchez‐de‐la‐Torre

Puig

et al. 2014

Gene

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“…Fracture risk OR for Gc2-2 = 0.32 (CI = 0.13–0.80) Compared to the other genotypes, none of the Gc2-2 individuals had any low energy fractures ( p = 0.021).Papiha et al86 2621United KingdomCaucasianGc1F, Gc1S, Gc2; Variable tandem (TAAA) n - Alu repeat in Intron8Intron 8* Alu repeat had significant association with lumbar spine and femoral neck BMD. BMD was observed to be lower in men with 10/8 genotype than 10/10 genotype ( p < 0.05).SarcoidosisMilman et al192 4444DenmarkCaucasian a Gc1F, Gc1S, Gc2NS Infections Diseases Human Immunodeficiency Virus (HIV)Alonso et al216 318 (at risk or infected)187SpainCaucasianGc1F, Gc1S, Gc2NSCleve et al217 971523United KingdomCaucasian a Gc1F, Gc1S, Gc2NSEales et al219 203 (at risk males)177 (50 homo-sexual and 122 hetero-sexual males)United KingdomCaucasian a Gc1F, Gc1S, Gc230% of AIDS patients were homozygous for Gc1F compared to 0.8% of controls ( p < 0.0001). Gc2-2 individuals were overrepresented in sero-negative contacts of AIDS patients ( p < 0.05).Pronk et al212 447 (96 AIDS patients and 351 homosexual men86NetherlandsCaucasian a Gc1F, Gc1S, Gc2NSPutkonen n et al218 125 (85 AIDS patients and 40 couples with 1 infected partner)3394SwedenCaucasian a Gc1F, Gc1S, Gc2N...…”

Section: Introductionmentioning

confidence: 99%

Common variants of the vitamin D binding protein gene and adverse health outcomes

Malik

Juras

et al. 2013

Critical Reviews in Clinical Laboratory Sciences

136

137

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The vitamin D binding protein (DBP) is the major plasma carrier for vitamin D and its metabolites, but it is also an actin scavenger, and is the precursor to the immunomodulatory protein, Gc-MAF. Two missense variants of the DBP gene – rs7041 encoding Asp432Glu and rs4588 encoding Thr436Lys – change the amino acid sequence and alter the protein function. They are common enough to generate population-wide constitutive differences in vitamin D status, based on assay of the serum metabolite, 25-hydroxyvitamin D (25OHD). Whether these variants also influence the role of vitamin D in an immunologic milieu is not known. However, the issue is relevant, given the immunomodulatory effects of DBP and the role of protracted innate immune-related inflammation in response to tissue injury or repeated infection. Indeed, DBP and vitamin D may jointly or independently contribute to a variety of adverse health outcomes unrelated to classical notions of their function in bone and mineral metabolism. This review summarizes the reports to date of associations between DBP variants, and various chronic and infectious diseases. The available information leads us to conclude that DBP variants are a significant and common genetic factor in some common disorders, and therefore, are worthy of closer attention. In view of the heightened interest in vitamin D as a public health target, well-designed studies that look simultaneously at vitamin D and its carrier in relation to genotypes and adverse health outcome should be encouraged.

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