Background: Continental Africa is facing an epidemic of chronic kidney disease (CKD). APOL1 risk variants have been shown to be strongly associated with an increased risk for non-diabetic kidney disease including HIV nephropathy, primary non-monogenic focal and segmental glomerulosclerosis, and hypertension-attributed nephropathy among African ancestry populations in the USA. The world's highest frequencies of APOL1 risk alleles have been reported in West African nations, overlapping regions with a high incidence of CKD and hypertension. One such region is south-eastern Nigeria, and therefore we sought to quantify the association of APOL1 risk alleles with CKD in this region. Methods: APOL1 risk variants were genotyped in a case-control sample set consisting of non-diabetic, CKD patients (n = 44) and control individuals (n = 43) from Enugu and Abakaliki, Nigeria. Results: We found a high frequency of two APOL1 risk alleles in the general population of Igbo people of south-eastern Nigeria (23.3%). The two APOL1 risk allele frequency in the CKD patient group was 66%. Logistic regression analysis under a recessive inheritance model showed a strong and significant association of APOL1 two-risk alleles with CKD, yielding an odds ratio of 6.4 (unadjusted p = 1.2E-4); following correction for age, gender, HIV and BMI, the odds ratio was 4.8 (adjusted p = 5.1E-03). Conclusion: APOL1 risk variants are common in the Igbo population of south-eastern Nigeria, and are also highly associated with non-diabetic CKD in this area. APOL1 may explain the increased prevalence of CKD in this region.

1.
Genovese G, Friedman DJ, Ross MD, et al: Association of trypanolytic APOL1 variants with kidney disease in African-Americans. Science 2010;329:841-845.
2.
Freedman BI, Langefeld CD: The new era of APOL1-associated glomerulosclerosis. Nephrol Dial Transplant 2012;27:1288-1291.
3.
Friedman DJ, Pollak MR: Genetics of kidney failure and the evolving story of APOL1. J Clin Invest 2011;121:3367-3374.
4.
Wasser WG, Tzur S, Wolday D, et al: Population genetics of chronic kidney disease: the evolving story of APOL1. J Nephrol 2012;25:603-618.
5.
Kopp JB, Nelson GW, Sampath K, et al: APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol 2011;22:2129-2137.
6.
Tzur S, Rosset S, Shemer R, et al: Missense mutations in the APOL1 gene are highly associated with end-stage kidney disease risk previously attributed to the MYH9 gene. Hum Genet 2010;128:345-350.
7.
Tzur S, Rosset S, Skorecki K, Wasser WG: APOL1 allelic variants are associated with lower age of dialysis initiation and thereby increased dialysis vintage in African- and Hispanic-Americans with non-diabetic end-stage kidney disease. Nephrol Dial Transplant 2012;27:1498-1505.
8.
Kanji Z, Powe CE, Wenger JB, et al: Genetic variation in APOL1 associates with younger age at hemodialysis initiation. J Am Soc Nephrol 2011;22:2091-2097.
9.
Papeta N, Kiryluk K, Patel A, et al: APOL1 variants increase risk for FSGS and HIVAN but not IgA nephropathy. J Am Soc Nephrol 2011;22:1991-1996.
10.
Lipkowitz MS, Freedman BI, Langefeld CD, et al: Apolipoprotein L1 gene variants associate with hypertension-attributed nephropathy and the rate of kidney function decline in African-Americans. Kidney Int 2013;83:114-120.
11.
Tayo BO, Kramer H, Salako BL, et al: Genetic variation in APOL1 and MYH9 genes is associated with chronic kidney disease among Nigerians. Int Urol Nephrol 2013;45:485-494.
12.
Behar DM, Rosset S, Tzur S, et al: African ancestry allelic variation at the MYH9 gene contributes to increased susceptibility to non-diabetic end-stage kidney disease in Hispanic-Americans. Hum Mol Genet 2010;19:1816-1827.
13.
Behar DM, Shlush LI, Maor C, Lorber M, Skorecki K: Absence of HIV-associated nephropathy in Ethiopians. Am J Kidney Dis 2006;47:88-94.
14.
Behar DM, Kedem E, Rosset S, et al: Absence of APOL1 risk variants protects against HIV-associated nephropathy in the Ethiopian population. Am J Nephrol 2011;34:452-459.
15.
US Renal Data System, USRDS 2010 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. Bethesda, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2010.
16.
Rosset S, Tzur S, Behar DM, Wasser WG, Skorecki K: The population genetics of chronic kidney disease: insights from the MYH9-APOL1 locus. Nat Rev Nephrol 2011;7:313-326.
17.
Ulasi II, Ijoma CK: The enormity of chronic kidney disease in Nigeria: the situation in a teaching hospital in South-East Nigeria. J Trop Med 2010;2010:501957.
18.
Ko W, Rajan P, Gomez F, et al: Identifying Darwinian Selection on Different Human APOL1 Variants among Diverse African Populations. Amer J Human Genetics 2013, .
19.
Twagirumukiza M, De Bacquer D, Kips JG, de Backer G, Stichele RV, Van Bortel LM: Current and projected prevalence of arterial hypertension in sub-Saharan Africa by sex, age and habitat: an estimate from population studies. J Hypertens 2011;29:1243-1252.
20.
Sumaili EK, Cohen EP, Zinga CV, Krzesinski JM, Pakasa NM, Nseka NM: High prevalence of undiagnosed chronic kidney disease among at-risk population in Kinshasa, the Democratic Republic of Congo. BMC Nephrol 2009;10:18.
21.
Ulasi II, Ijoma CK, Onwubere BJ, Arodiwe E, Onodugo O, Okafor C: High prevalence and low awareness of hypertension in a market population in Enugu, Nigeria. Int J Hypertens 2011; Article ID 869675; doi:10.4061/2011/869675.
22.
Cooper R, Rotimi C, Ataman S, et al: The prevalence of hypertension in seven populations of West African origin. Am J Public Health 1997;87:160-168.
23.
Ulasi II, Arodiwe EB, Ijoma CK: Left ventricular hypertrophy in African Black patients with chronic renal failure at first evaluation. Ethn Dis 2006;16:859-864.
24.
Atta MG, Estrella MM, Kuperman M, et al: HIV-associated nephropathy patients with and without apolipoprotein L1 gene variants have similar clinical and pathological characteristics. Kidney Int 2012;82:338-343.
25.
Odubanjo MO, Okolo CA, Oluwasola AO, Arije A: End-stage renal disease in Nigeria: an overview of the epidemiology and the pathogenetic mechanisms. Saudi J Kidney Dis Transpl 2011;22:1064-1071.
26.
Arogundade FA, Sanusi AA, Hassan MO, Akinsola A: The pattern, clinical characteristics and outcome of ESRD in Ile-Ife, Nigeria: is there a change in trend? Afr Health Sci 2011;11:594-601.
27.
World Health Organization: Fact Sheet No. 259: Human African trypanosomiasis. http://www.whoint/mediacentre/factsheets/fs259/en/ (accessed on August 9, 2012).
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