- 作者: María Ángeles JIMÉNEZ-SOUSA, José Luis JIMÉNEZ, Amanda FERNÁNDEZ-RODRÍGUEZ, José María BELLÓN, Carmen RODRÍGUEZ, Melchor RIERA, Joaquín PORTILLA, Ángeles CASTRO, María Ángeles MUÑOZ-FERNÁNDEZ and Salvador RESINO
- 作者服務機構: 1. Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda- Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain 2. Plataforma de Laboratorio, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain 3. Fundación para la Investigación Biomédica, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain 4. Centro Sanitario Sandoval, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain 5. Servicio de Medicina Interna-Infecciosas, Hospital Universitario “Son Espases”, Palma de Mallorca, Spain 6. Servicio de Enfermedades Infecciosas, Hospital General Universitario de Alicante, Alicante, Spain 7. Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Complejo Hospitalario Universitario a Coruña (CHUAC), A Coruña, Spain 8. Sección Inmunología, Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, IiSGM, and Spanish HIV HGM BioBank, Madrid, Spain 9. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain 10. Mª. Ángeles MUÑOZ-FERNÁNDEZ and Salvador RESINO contributed equally to this work.
- 中文摘要:
- 英文摘要:
Background
Most of the circulating Vitamin D (VitD) is transported bound to vitamin D-binding protein (DBP), and several DBP single nucleotide polymorphisms (SNPs) have been related to circulating VitD concentration and disease. In this study, we evaluated the association among DBP SNPs and AIDS progression in antiretroviral treatment (ART)-naïve-HIV-infected patients.
Methods
We performed a retrospective study in 667 patients who were classified according to their pattern of AIDS progression (183 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 150 rapid progressors (RPs)) and 113 healthy blood donors (HIV, HCV, and HBV negative subjects). We genotyped seven DBP SNPs (rs16846876, rs12512631, rs2070741, rs2282679, rs7041, rs1155563, rs2298849) using Agena Bioscience’s MassARRAY platform. The genetic association was evaluated by Generalized Linear Models adjusted by age at the moment of HIV diagnosis, gender, risk group, and VDR rs2228570 SNP. Multiple testing correction was performed by the false discovery rate (Benjamini and Hochberg procedure; q-value).
Results
All SNPs were in HWE (p > 0.05) and had similar genotypic frequencies for DBP SNPs in healthy-controls and HIV-infected patients. In unadjusted GLMs, we only found significant association with AIDS progression in rs16846876 and rs12512631 SNPs. In adjusted GLMs, DBP rs16846876 SNP showed significant association under the recessive inheritance model [LTNPs vs. RPs (adjusted odds ratio (aOR) = 3.53; q-value = 0.044) and LTNPs vs. MPs (aOR = 3.28; q-value = 0.030)] and codominant [LTNPs vs. RPs (aOR = 4.92; q-value = 0.030) and LTNPs vs. MPs (aOR = 3.15; q-value = 0.030)]. Also, we found DBP rs12512631 SNP showed significant association in the inheritance model dominant [LTNPs vs. RPs (aOR = 0.49; q-value = 0.031) and LTNPs vs. MPs (aOR = 0.6; q-value = 0.047)], additive [LTNPs vs. RPs (aOR = 0.61; q-value = 0.031)], overdominant [LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)], and codominant [LTNPs vs. RPs (aOR = 0.52; q-value = 0.036) and LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)]. Additionally, we found a significant association between DBP haplotypes (composed by rs16846876 and rs12512631) and AIDS progression (LTNPs vs RPs): DBP haplotype AC (aOR = 0.63; q-value = 0.028) and the DBP haplotype TT (aOR = 1.64; q-value = 0.028).
Conclusions
DBP rs16846876 and rs12512631 SNPs are related to the patterns of clinical AIDS progression (LTNP, MP, and RP) in ART-naïve HIV-infected patients. Our findings provide new knowledge about AIDS progression that may be relevant to understanding the pathogenesis of HIV infection. - 中文關鍵字:
- 英文關鍵字: Single nucleotide polymorphisms, DBP, LTNPs, AIDS, Non-progression