Vitamin D-related Host Genetic Variants Alter HIV Disease Progression in Children

被引:21
作者
Moodley, Amaran [1 ,2 ]
Qin, Min [3 ]
Singh, Kumud K. [1 ,2 ]
Spector, Stephen A. [1 ,2 ]
机构
[1] Univ Calif San Diego, San Diego, CA 92103 USA
[2] Rady Childrens Hosp, San Diego, CA USA
[3] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
vitamin D; HIV; vitamin D receptor; pediatric AIDS; host genetics; D-RECEPTOR GENE; IMMUNODEFICIENCY-VIRUS-INFECTION; SERUM 25-HYDROXYVITAMIN D; D DEFICIENCY; THERAPY-NAIVE; ASSOCIATION; POLYMORPHISM; SUPPLEMENTATION; TUBERCULOSIS; PREVALENCE;
D O I
10.1097/INF.0b013e31829e4d06
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Vitamin D deficiency is common in HIV infection and has been associated with advanced disease. This study investigated whether vitamin D-related genetic variants were associated with disease progression in HIV-infected children. Methods: The Fok-I (C/T), Bsm-I (G/A), GC (A/C), DHCR7 (G/T) and CYP2R1 (G/A) genetic variants were detected by real-time polymerase chain reaction in HIV-infected children who participated in the Pediatric AIDS Clinical Trials Group P152 and P300 protocols, which predated the availability of effective combination antiretroviral therapy. The primary endpoints included time to progression to the first HIV-related disease endpoint (>= 2 opportunistic infection, weight growth failure) or death, which constituted the progression-free survival. Analyses were performed for age >2 years and <= 2 years separately adjusting for race and treatment effect. Results: Of the 998 children evaluated, 139 experienced HIV disease progression. For children >2 years, rapid disease progression was associated with the DHCR7 G allele compared with the T allele (G/G vs. T/T: hazard ratio [HR] = 5.0, P = 0.035; G/T vs. T/T: HR = 4.5, P = 0.042; G/G+G/T vs. T/T: HR = 4.8, P = 0.036) and the Bsm-I A allele compared with the G allele (A/G vs. G/G: HR = 2.2, P = 0.014 and A/G+A/A vs. G/G: HR = 2.0, P = 0.026). In children = 2 years, the Bsm-I A allele increased the risk of disease progression in Hispanics (A/A vs. G/A+G/G: HR = 2.8, P = 0.03 and A/A vs. G/G: HR = 2.8, P = 0.046) and whites (A/A vs. G/G: HR = 6.6, P = 0.025 and A/A vs. G/A+G/G: HR = 3.6, P = 0.038). Conclusions: Vitamin D-related host genetic variants that alter the availability and activity of vitamin D are associated with risk of HIV disease progression in children and may vary by age and race.
引用
收藏
页码:1230 / 1236
页数:7
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