Dataset Information

Genetic variation in APOL1 and MYH9 genes is associated with chronic kidney disease among Nigerians.

ABSTRACT:

Purpose

A region of chromosome 22 which includes APOL1 and MYH9 genes was recently identified as a risk locus for non-diabetic forms of kidney disease, including idiopathic and HIV-associated focal segmental glomerular sclerosis and kidney disease clinically attributed to hypertension among African Americans. The purposes of the current study were, therefore, to examine the frequency of these variants and to determine whether they are associated with chronic kidney disease (CKD) among native Africans.

Methods

To investigate the possible evidence of association between variants in these genes and non-diabetic CKD among West Africans, we performed a case/control analysis in a sample of 166 Nigerians without history of European admixture. Our study included a total of 9 variants on APOL1 (n = 4) and MYH9 (n = 5) genes.

Results

We observed significantly strong associations with previously reported APOL1 variants rs73885319 and rs60910145, and their two-allele "G1" haplotype (P < 0.005). We did not observe significant evidence of association between non-diabetic CKD and any of the MYH9 variants or haplotypes after accounting for multiple testing in our sample.

Conclusions

In conclusion, APOL1 risk variants are associated with non-diabetic forms of CKD among Nigerians of Yoruba ethnicity. Further information on APOL1/MYH9 variants may lead to screening programs, which could lead to earlier detection and interventions for non-diabetic kidney disease.

SUBMITTER: Tayo BO

PROVIDER: S-EPMC3599169 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Publications

Genetic variation in APOL1 and MYH9 genes is associated with chronic kidney disease among Nigerians.

Tayo Bamidele O BO Kramer Holly H Salako Babatunde L BL Gottesman Omri O McKenzie Colin A CA Ogunniyi Adesola A Bottinger Erwin P EP Cooper Richard S RS

International urology and nephrology 20120907 2

<h4>Purpose</h4>A region of chromosome 22 which includes APOL1 and MYH9 genes was recently identified as a risk locus for non-diabetic forms of kidney disease, including idiopathic and HIV-associated focal segmental glomerular sclerosis and kidney disease clinically attributed to hypertension among African Americans. The purposes of the current study were, therefore, to examine the frequency of these variants and to determine whether they are associated with chronic kidney disease (CKD) among na ...[more]

PMID: 22956460

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Project description:IntroductionAlthough environmental exposure to hydrocarbons has been linked to non-communicable diseases, its association with chronic kidney disease (CKD) is still an emerging area. Epidemiological studies associating CKD with prolonged exposure to hydrocarbons have mostly focused on occupational exposure, with fewer studies on environmental exposure from residing in contaminated areas. The aim of this study was to determine any association between long-term exposure to petrochemical products and the risk of CKD by comparing the residence and occupational history of young patients with CKD and non-CKD controls.Materials and methodsA case-control study of 74 cases and 74 age- and sex-matched non-CKD controls was carried out. Cases were patients with CKD who were aged 18-44 years and diagnosed with suspected chronic glomerulonephritis (CGN). Patients were recruited from an outpatient nephrology clinic and medical wards. Patients with CKD from traditional causes were excluded. Data were collected using a pre-tested structured questionnaire adapted from the WHO STEPwise approach to the non-communicable disease risk factor surveillance (STEPS) instrument. To assess exposure, a detailed work history and all residential addresses where the patients have lived for at least 5 years were recorded. 'Exposed' status was regarded as long-term residence in a known oil-polluted area and jobs involving crude oil exploration, processing, transportation and sales, and cleanup of crude oil hazards. Absence of a history of chronic exposure or any form of exposure was regarded as 'less exposed'.ResultsThere were 52 (70.3%) cases categorized as exposed, compared with 21 (28.4%) controls (p < 0.001). There were 34 (45.9%) cases born near petrochemical refineries and plants, compared with 11 (14.9%) controls (p ≤ 0.001). There were 34 (45.9%) cases residing near petrochemical refineries and plants, compared with 8 (10.9%) controls (p ≤ 0.001). When asked 'Do you think you have been significantly exposed to crude oil?', 15 (20.3%) cases and 2 (2.7%) controls answered 'yes' (p ≤ 0.001).ConclusionOur findings suggest an association between exposure to petrochemicals and CKD in young Nigerians diagnosed with suspected CGN. Exposure is significantly associated with a higher mean age, waist circumference, and blood sugar levels; however, other traditional risk factors for CKD were not considerably more prevalent in this unique patient population. These findings should prompt more emphasis on occupational history, residential history, and other relevant environmental exposures in the assessment of patients at risk for CKD.

Project description:MYH9 has been proposed as a major genetic risk locus for a spectrum of nondiabetic end stage kidney disease (ESKD). We use recently released sequences from the 1000 Genomes Project to identify two western African-specific missense mutations (S342G and I384M) in the neighboring APOL1 gene, and demonstrate that these are more strongly associated with ESKD than previously reported MYH9 variants. The APOL1 gene product, apolipoprotein L-1, has been studied for its roles in trypanosomal lysis, autophagic cell death, lipid metabolism, as well as vascular and other biological activities. We also show that the distribution of these newly identified APOL1 risk variants in African populations is consistent with the pattern of African ancestry ESKD risk previously attributed to MYH9.Mapping by admixture linkage disequilibrium (MALD) localized an interval on chromosome 22, in a region that includes the MYH9 gene, which was shown to contain African ancestry risk variants associated with certain forms of ESKD (Kao et al. 2008; Kopp et al. 2008). MYH9 encodes nonmuscle myosin heavy chain IIa, a major cytoskeletal nanomotor protein expressed in many cell types, including podocyte cells of the renal glomerulus. Moreover, 39 different coding region mutations in MYH9 have been identified in patients with a group of rare syndromes, collectively termed the Giant Platelet Syndromes, with clear autosomal dominant inheritance, and various clinical manifestations, sometimes also including glomerular pathology and chronic kidney disease (Kopp 2010; Sekine et al. 2010). Accordingly, MYH9 was further explored in these studies as the leading candidate gene responsible for the MALD signal. Dense mapping of MYH9 identified individual single nucleotide polymorphisms (SNPs) and sets of such SNPs grouped as haplotypes that were found to be highly associated with a large and important group of ESKD risk phenotypes, which as a consequence were designated as MYH9-associated nephropathies (Bostrom and Freedman 2010). These included HIV-associated nephropathy (HIVAN), primary nonmonogenic forms of focal segmental glomerulosclerosis, and hypertension affiliated chronic kidney disease not attributed to other etiologies (Bostrom and Freedman 2010). The MYH9 SNP and haplotype associations observed with these forms of ESKD yielded the largest odds ratios (OR) reported to date for the association of common variants with common disease risk (Winkler et al. 2010). Two specific MYH9 variants (rs5750250 of S-haplotype and rs11912763 of F-haplotype) were designated as most strongly predictive on the basis of Receiver Operating Characteristic analysis (Nelson et al. 2010). These MYH9 association studies were then also extended to earlier stage and related kidney disease phenotypes and to population groups with varying degrees of recent African ancestry admixture (Behar et al. 2010; Freedman et al. 2009a, b; Nelson et al. 2010), and led to the expectation of finding a functional African ancestry causative variant within MYH9. However, despite intensive efforts including re-sequencing of the MYH9 gene no suggested functional mutation has been identified (Nelson et al. 2010; Winkler et al. 2010). This led us to re-examine the interval surrounding MYH9 and to the detection of novel missense mutations with predicted functional effects in the neighboring APOL1 gene, which are significantly more associated with ESKD than all previously reported SNPs in MYH9.

Project description:BackgroundAmong patients in the United States with chronic kidney disease, black patients are at increased risk for end-stage renal disease, as compared with white patients.MethodsIn two studies, we examined the effects of variants in the gene encoding apolipoprotein L1 (APOL1) on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), we evaluated 693 black patients with chronic kidney disease attributed to hypertension. In the Chronic Renal Insufficiency Cohort (CRIC) study, we evaluated 2955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) according to whether they had 2 copies of high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group). In the AASK study, the primary outcome was a composite of end-stage renal disease or a doubling of the serum creatinine level. In the CRIC study, the primary outcomes were the slope in the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline.ResultsIn the AASK study, the primary outcome occurred in 58.1% of the patients in the APOL1 high-risk group and in 36.6% of those in the APOL1 low-risk group (hazard ratio in the high-risk group, 1.88; P<0.001). There was no interaction between APOL1 status and trial interventions or the presence of baseline proteinuria. In the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes (P<0.001 for all comparisons).ConclusionsRenal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

Dataset Information

Genetic variation in APOL1 and MYH9 genes is associated with chronic kidney disease among Nigerians.

Purpose

Methods

Results

Conclusions

Publications

Genetic variation in APOL1 and MYH9 genes is associated with chronic kidney disease among Nigerians.

Similar Datasets

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