Nine genetic studies in African-Americans with lupus
| Author, year | N | Objective | Results | Conclusions | Level of evidence |
|---|---|---|---|---|---|
| Larsen et al, 201363 | 546 | To investigate whether APOL1 risk alleles associate with SLE-associated CG | Evaluation of biopsies from 188 cases with zero risk alleles, 264 cases with one risk allele and 94 cases with two risk alleles revealed 26 cases with CG, and APOL1 was strongly associated with SLE-associated CG (p<0.001). | APOL1 genotyping of African-American patients with SLE might help identify patients at risk for CG, a phenomenon with a poor prognosis often resistant to treatment | III |
| Freedman et al, 201464 | 1389 | To investigate whether the APOL1 nephropathy risk alleles G1/G2, common in African-Americans and rare in European Americans, contribute to the ethnic disparity in risk | Two risk alleles, G1/G2, were strongly associated with SLE-ESRD, with 25% of cases and 12% of controls having two nephropathy alleles (OR 2.57, recessive model p=1.49×10−9). The population-attributable risk (adjusted for age, sex and admixture) for ESRD among patients with G1/G2 polymorphisms was 0.26 compared with 0.003 among European American patients. The mean time from SLE diagnosis to ESRD development was about 2 years earlier among individuals with APOL1 risk genotypes (p=0.01). | The high frequency of APOL1 G1/G2 alleles in African-Americans with near absence in European Americans explains an important proportion of the increased risk of LN-ESRD in African-Americans | III |
| Namjou et al, 201265 | 5 | To assess and characterise C1q deficiency in an African-American lupus pedigree | A novel homozygote start codon mutation in C1qA gene that changes amino acid methionine to arginine at position 1 (Met1Arg) was identified in an African-American patient with lupus and C1q deficiency and her family members, along with absence of total complement activity consistent with a recessive pattern of inheritance. | The identification of new mutation in C1qA gene that disrupts the start codon (ATG to AGG (Met1Arg)) expands the knowledge and importance of the C1q gene in the pathogenesis of lupus in the high-risk African-American population | III |
| Ramos et al, 201366 | 3364 | To analyse variation in reactive intermediate genes for association with SLE in two populations with African ancestry | The glutathione reductase gene GSR (rs2253409; p=0.0014, OR 1.26, 95% CI 1.09 to 1.44) was the most significant single SNP association in African-Americans. In the Gullah, the NADH dehydrogenase NDUFS4 (rs381575; p=0.0065, OR 2.10, 95% CI 1.23 to 3.59) and NO synthase gene NOS1 (rs561712; p=0.0072, OR 0.62, 95% CI 0.44 to 0.88) were most strongly associated with SLE. When both populations were analysed together, GSR remained the most significant effect (rs2253409; p=0.00072, OR 1.26, 95% CI 1.10 to 1.44). | Results suggest distinct patterns of association with SLE in African-derived populations | III |
| Ruiz-Narvaez et al, 201167 | 1148 | To conduct a screening of the MHC region for SNPs and the deletion of the C4A gene in a SLE case–control study | The rs9271366 SNP was most strongly associated with SLE (OR, OR=1.70, p=5.6×10−5). Conditional haplotype analysis revealed three other SNPs, rs204890 (OR=1.86, p=1.2×10−4), rs2071349 (OR=1.53, p=1.0×10−3), and rs2844580 (OR=1.43, p=1.3×10−3) to be associated with SLE independent of the rs9271366 SNP. A genotype score combining the four newly identified SNPs showed an additive risk according to the number of high-risk alleles (OR=1.67 per high-risk allele, p<0.0001). | There are four independent signals in the MHC region associated with risk of SLE in African-American women | III |
| Sánchez et al, 201168 | 3748 | To examine whether some of the same susceptibility loci increase lupus risk in African-American individuals | Authors found the first evidence of genetic association between lupus in African-American patients and five susceptibility loci (C8orf13-BLK, BANK1, TNFSF4, KIAA1542 and CTLA4; p=8.0×10−6, p=1.9×10−5, p=5.7×10−5, p=0.00099, and p=0.0045, respectively). Authors also confirmed the genetic association between lupus and five additional lupus susceptibility loci (ITGAM, MSH5, CFB, STAT4 and FCGR2A; p=7.5×10−11, p=5.2×10−8, p=8.7×10−7, p=0.0058, and p=0.0070, respectively), and provided evidence of genome-wide significance for the association between lupus in African-American patients and ITGAM and MSH5 (HLA region). | Novel genetic susceptibility loci for lupus were identified in African-Americans and authors demonstrated that the majority of lupus susceptibility loci examined confer lupus risk across multiple ethnicities | III |
| Dozmorov et al, 201370 | 40 | To study the higher rates of lupus-related ESRD in African-Americans | A strong link was detected between APOL1 G1 and G2 variants and LN-ESRD in African-Americans. | Findings further support the role of G1 and G2 variants of APOL1 gene in higher rates of lupus-related ESRD in African-Americans | III |
| Wu et al, 200372 | 361 | To explore the −844C genotype in African-Americans with SLE | There was enrichment of the –844C homozygous genotype in the patients with SLE compared with ethnically matched controls. | Findings further support the potential importance of SNPs in regulatory regions | III |
| Freedman et al, 201369 | N/A | To review the current status of APOL1-associated nephropathy | There is a genetic association between the APOL1 gene and several severe non-diabetic forms of kidney disease in African-Americans that nears Mendelian inheritance patterns. This associated accounts for and account for a large percentage of glomerulosclerosis in populations of African ancestry. | Emerging data support an important role for APOL1 in the progression of kidney disease | V |
APOL1, apolipoprotein L1; CG, collapsing glomerulopathy; ESRD, end-stage renal disease; HLA, human leukocyte antigen; LN, lupus nephritis; MHC, major histocompatibility complex; N/A, not available; SLE, systemic lupus erythematosus; SNP, single-nucleotide polymorphism.