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该基因中的功能单倍型与肯尼亚未接受过抗逆转录病毒治疗和有抗逆转录病毒治疗经验的注射吸毒感染HIV-1者的体重过轻、免疫抑制及病毒抑制相关。

Functional Haplotypes in the Gene are Associated with Underweight, Immunosuppression and Viral Suppression in Kenyan HIV-1 Infected Antiretroviral Treatment Naive and Experienced Injection Substance Users.

作者信息

Nathan Shaviya, Valentine Budambula, Tom Were

机构信息

Department of Medical Laboratory Sciences, Masinde Muliro University of Science and Technology, Kakamega, Kenya.

Department of Environmental Health, Technical University of Mombasa, Kenya.

出版信息

Ethiop J Health Sci. 2020 Jul 1;30(4):489-500. doi: 10.4314/ejhs.v30i4.4.

DOI:10.4314/ejhs.v30i4.4
PMID:33897209
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8054454/
Abstract

BACKGROUND

Human immunodeficiency virus and injection substance use have an influence on genes and gene expression. These effects could be beneficial or detrimental in defining disease outcomes. Adiponectin gene is key in modulating metabolic and immunoregulatory functions. Understanding the effects of human immunodeficiency virus and injection substance use on the gene in the context of antiretroviral therapy is important for predicting disease outcomes.

METHODS

This cross-sectional genetic study determined polymorphisms in the promoter region of adiponectin gene. Two variants were analyzed: rs2241766 and rs266729. Polymorphisms were associated with clinical markers of disease outcome; underweight, immunosuppression and viral suppression. The variants were genotyped via random fragment length polymorphism.

RESULT

GC haplotype was associated with higher odds of having underweight (OR, 2.21; 95% CI, 1.83-4.60; P=0.008 OR, 2.30; 95% CI, 1.89-4.71; P=0.006) in antiretroviral treatment - naive and experienced injection substance users and immunosuppression (OR, 1.90; 95% CI 1.67-3.98, P=0.041) in naive. Bonferroni correction revealed GC haplotype carriers only to have low body mass index in both naive (median, 14.8; IQR, 3.2 kg/m; P=0.002) and experienced (median, 15.2; IQR, 3.2 kg/m; P=0.002) injection substance users. Circulating total adiponectin levels were higher in naive (median, 19.5; IQR, 7.9 µg/ml) than - experienced (median, 12.0; IQR, 4.4 µg/ml) injection substance users (P=0.0001). GC carriers presented with low serum adiponectin levels in both study groups.

CONCLUSION

The study revealed haplotypes of adiponectin gene at loci rs2241766 and rs266729 that could determine disease outcomes in human immunodeficiency virus -1 antiretroviral treatment- naive and experienced injection substance users.

摘要

背景

人类免疫缺陷病毒和注射吸毒对基因及基因表达有影响。这些影响在确定疾病转归方面可能是有益的或有害的。脂联素基因在调节代谢和免疫调节功能中起关键作用。了解人类免疫缺陷病毒和注射吸毒在抗逆转录病毒治疗背景下对该基因的影响对于预测疾病转归很重要。

方法

这项横断面基因研究确定了脂联素基因启动子区域的多态性。分析了两个变体:rs2241766和rs266729。多态性与疾病转归的临床标志物相关;体重过轻、免疫抑制和病毒抑制。通过随机片段长度多态性对变体进行基因分型。

结果

在初治和有抗逆转录病毒治疗经验的注射吸毒者中,GC单倍型与体重过轻的较高几率相关(比值比,2.21;95%置信区间,1.83 - 4.60;P = 0.008;比值比,2.30;95%置信区间,1.89 - 4.71;P = 0.006),在初治者中与免疫抑制相关(比值比,1.90;95%置信区间1.67 - 3.98,P = 0.041)。Bonferroni校正显示,在初治(中位数,14.8;四分位距,3.2 kg/m²;P = 0.002)和有经验的(中位数,15.2;四分位距,3.2 kg/m²;P = 0.002)注射吸毒者中,GC单倍型携带者的体重指数均较低。初治注射吸毒者(中位数,19.5;四分位距,7.9 μg/ml)的循环总脂联素水平高于有经验的(中位数,12.0;四分位距,4.4 μg/ml)注射吸毒者(P = 0.0001)。在两个研究组中,GC携带者的血清脂联素水平均较低。

结论

该研究揭示了脂联素基因在rs2241766和rs266729位点的单倍型,这些单倍型可能决定人类免疫缺陷病毒1型初治和有抗逆转录病毒治疗经验的注射吸毒者的疾病转归。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f26/8054454/9eeb65384e73/EJHS3004-0489Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f26/8054454/58b300eb2639/EJHS3004-0489Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f26/8054454/ab889ae5eb85/EJHS3004-0489Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f26/8054454/9eeb65384e73/EJHS3004-0489Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f26/8054454/58b300eb2639/EJHS3004-0489Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f26/8054454/ab889ae5eb85/EJHS3004-0489Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f26/8054454/9eeb65384e73/EJHS3004-0489Fig3.jpg

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