RESUMO
Variants in the Apolipoprotein L1 (APOL1) gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two APOL1 risk alleles, a role in HIV infectivity has been postulated in the mechanism of APOL1 associated kidney disease. Herein, we aim to explore the association between HIV viremia and APOL1 genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two APOL1 renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89-40.8, p < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49-13.15, p = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0-5.63, p = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66-33.35, P = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12-0.98, p = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of APOL1 variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.
RESUMO
BACKGROUND: Chronic kidney disease (CKD) is a significant comorbidity among hypertensive patients. Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9) have been demonstrated to be significantly associated with CKD, among African- and European-derived populations. We investigated the spectrum of MYH9-associated CKD among Ghanaian hypertensive patients. METHODS: The study constituted a total of 264 hypertensive patients. Hypertensive patients with glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 (CKD-EPI formula) or clinically diagnosed were defined as case subjects (n = 132) while those with eGFR ≥60 ml/min/1.73m2 were classified as control subjects (n = 132). Demographic data were obtained with a questionnaire and anthropometric measurements were taken. Five (5) millilitres (ml) of venous blood was drawn from study subjects into gel and EDTA vacutainer tubes. Two (2) mL of EDTA anticoagulated blood was used for genomic DNA extraction while three (3) mL of blood was processed to obtain serum for biochemical measurements. Genotyping of MYH9 polymorphisms (rs3752462) was done employing Tetra primer Amplification Refractory Mutation System (T-ARMS) polymerase chain reaction (PCR). Spot urine samples were also collected for urinalysis. Hardy-Weinberg population was assessed. Logistic regression models were used to assess the associations between single nucleotide polymorphisms and CKD. RESULTS: The cases and control participants differed in terms of age, sex, family history, and duration of CKD (p-value < 0.001). The minor allele frequencies of rs3752462 SNP were 0.820 and 0.567 respectively among the control and case subjects. Patients with the heterozygote genotype of rs3752462 (CT) were more likely to develop CKD [aOR = 7.82 (3.81-16.04)] whereas those with homozygote recessive variant (TT) were protective [aOR = 0.12 (0.06-0.25)]. Single nucleotide polymorphism of rs3752462 (CT genotype) was associated with increased proteinuria, albuminuria, and reduced eGFR. CONCLUSIONS: We have demonstrated that MYH9 polymorphisms exist among Ghanaian hypertensive patients and rs3752462 polymorphism of MYH9 is associated with CKD. This baseline indicates that further longitudinal and multi-institutional studies in larger cohorts in Ghana are warranted to evaluate MYH9 SNP as an independent predictor of CKD among hypertensive patients in Ghana.
RESUMO
Dyslipidemia is a potential complication of long-term usage of antiretroviral therapy (ART) and also known to be associated with genetic factors. The host genetic variants associated with dyslipidemia in HIV patients on ART in Ghana have not been fully explored. The study constituted a total of 289 HIV-infected patients on stable ART for at least a year. Fasting blood was collected into EDTA tube for lipids measurement. Lipid profiles were used to define dyslipidemia based on the NCEP-ATP III criteria. HIV-infected subjects were categorized into two groups; those with dyslipidemia (cases) (n = 90; 31.1%) and without dyslipidemia (controls)(n = 199; 68.9%). Four candidate single nucleotide polymorphism (SNP) genes (ABCA1-rs2066714, LDLR-rs6511720, APOA5-rs662799 and DSCAML1-rs10892151) were determined. Genotyping was performed on isolated genomic DNA of study participants using PCR followed by a multiplex ligation detection reaction (LDR). The percentage of the population who had the rare homozygote alleles for rs6511720 (T/T), rs2066714 (G/G), rs10892151 (T/T) and rs662799 (G/G) among case subjects were 5.5%, 14.4%, 6.6% and 10.0% whiles 2.0% 9.1%, 6.5% and 4.0% were observed among control subjects. There were statistically significant differences in the genotypic prevalence of APOA5 (p = 0.0357) and LDLR polymorphisms (p = 0.0387) between case and control subjects. Compared to the AA genotype of the APOA5 polymorphisms, individuals with the rare homozygote genotype [aOR = 2.38, 95%CI(1.06-6.54), p = 0.004] were significantly associated with an increased likelihood of developing dyslipidemia after controlling for age, gender, treatment duration, CD4 counts and BMI. Moreover, individuals with the rare homozygous genotype of ABCA1 (G/G) [aOR = 10.7(1.3-88.7), p = 0.0280] and LDLR (rs6511720) G>T [aOR = 61.2(7.6-493.4), p<0.0001) were more likely to have high levels of total cholesterol levels. Our data accentuate the presence of SNPs in four candidate genes and their association with dyslipidemia among HIV patients exposed to ART in the Ghanaian population, especially variants in APOA5-rs662799 and LDLR rs6511720 respectively. These findings provide baseline information that necessitates a pre-symptomatic strategy for monitoring dyslipidemia in ART-treated HIV patients. There is a need for longitudinal studies to validate a comprehensive number of SNPs and their associations with dyslipidemia.
