| 1. |
- Wang, Zhaoming, et al.
(författare)
-
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
|
|
| 2. |
- Delanaye, Pierre, et al.
(författare)
-
Performance of creatinine-based equations to estimate glomerular filtration rate in White and Black populations in Europe, Brazil, and Africa
- 2022
-
Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 38:1, s. 106-118
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A new Chronic Kidney Disease Epidemiology equation without race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared to the new European Kidney Function Consortium (EKFC) and Lund-Malmö Revised (LMREV) equations, developed in European cohorts.METHODS: Standardized creatinine and measured glomerular filtration rate (GFR) from the European EKFC cohorts (n = 13 856 including 6031 individuals in the external validation cohort), from France, (n = 4429, including 964 Black Europeans), from Brazil (n = 100), and from Africa (n = 508) were used to test the performances of the equations. A matched analysis between White Europeans and Black Africans or Black Europeans was performed.RESULTS: In White Europeans (n = 9496), both the EKFC and LMREV equations outperformed CKD-EPIAS (bias of -0.6 and -3.2, respectively versus 5.0 mL/min/1.73m², and accuracy within 30% of 86.9 and 87.4, respectively versus 80.9%). In Black Europeans and Black Africans, the best performance was observed with the EKFC equation using a specific Q-value ( = concentration of serum creatinine in healthy males and females). These results were confirmed in matched analyses, which showed that serum creatinine concentrations were different in White Europeans, Black Europeans, and Black Africans for the same measured GFR, age, sex and body mass index. Creatinine differences were more relevant in males.CONCLUSION: In a European and African cohort, the performances of CKD-EPIAS remain suboptimal. The EKFC equation, using usual or dedicated, population-specific Q-values presents the best performance in the whole age range in the European and African populations included in this study.
|
|
| 3. |
- Berg, Ulla B., et al.
(författare)
-
New standardized cystatin C and creatinine GFR equations in children validated with inulin clearance
- 2015
-
Ingår i: Pediatric Nephrology. - : Springer Science and Business Media LLC. - 1432-198X .- 0931-041X. ; 30:8, s. 1317-1326
-
Tidskriftsartikel (refereegranskat)abstract
- This study compares glomerular filtration rate (GFR) equations in children based on standardized cystatin C (CYSC) and creatinine (CREA) and their combinations with renal clearance of inulin (C-inulin). A total of 220 children with different renal disorders were referred for C-inulin (median 84 ml/min/1.73 m(2)). Bias, precision (interquartile range, IQR), and accuracy (percentage of estimates +/- 30 % of C-inulin; P30) were evaluated for two cystatin C equations, CAPA(CYSC) and Berg(CYSC), for creatinine equations, Schwartz(CREA) and Gao(CREA), the arithmetic mean of CAPA(CYSC) and Schwartz(CREA) (MEAN(CAPA+Schwartz)), Berg(CYSC) and Schwartz(CREA) (MEAN(BERG+SCHWARTZ)) and the composite equation Chehade(CYSC+CREA). Overall results of CAPA(CYSC), Berg(CYSC), Schwartz(CREA), Gao(CREA), MEAN(CAPA+Schwartz,) MEAN(BERG+SCHWARTZ) and Chehade(CYSC+CREA) were: median bias -7.6/-4.9/-3.7/-2.3/-4.6/-4.0/-10.1 %, IQR 20.0/19.9/21.7/22.4/21.0/20.9/23.3 ml/min/1.73 m(2) and P30 86/86/80/83/89/91/83 %. The cystatin C equations, MEAN(CAPA+Schwartz) and MEAN(BERG+SCHWARTZ) had a more stable performance across subgroups compared with Schwartz(CREA), Gao(CREA) and Chehade(CYSC+CREA). Cystatin C was the preferred filtration marker for GFR estimation in children, while the benefit of combining cystatin C and creatinine deserves further investigations.
|
|
| 4. |
|
|
| 5. |
- Soveri, Inga, et al.
(författare)
-
Measuring GFR: A Systematic Review.
- 2014
-
Ingår i: American Journal of Kidney Diseases. - : Elsevier BV. - 1523-6838 .- 0272-6386. ; 64:3, s. 411-424
-
Tidskriftsartikel (refereegranskat)abstract
- Background No comprehensive systematic review of the accuracy of glomerular filtration rate (GFR) measurement methods using renal inulin clearance as reference has been published. Study Design Systematic review with meta-analysis of cross-sectional diagnostic studies. Setting & Population Published original studies and systematic reviews in any population. Selection Criteria for Studies Index and reference measurements conducted within 48 hours; at least 15 participants studied; GFR markers measured in plasma or urine; plasma clearance calculation algorithm verified in another study; tubular secretion of creatinine had not been blocked by medicines. Index Tests Endogenous creatinine clearance; renal or plasma clearance of chromium 51−labeled ethylenediaminetetraacetic acid (51Cr-EDTA), diethylenetriaminepentaacetic acid (DTPA), iohexol, and iothalamate; and plasma clearance of inulin. Reference Test Renal inulin clearance measured under continuous inulin infusion and urine collection. Results Mean bias < 10%, median bias < 5%, the proportion of errors in the index measurements that did not exceed 30% (P30) ≥ 80%, and P10 ≥ 50% were set as requirements for sufficient accuracy. Based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, the quality of evidence across studies was rated for each index method. Renal clearance of iothalamate measured GFR with sufficient accuracy (strong evidence). Renal and plasma clearance of 51Cr-EDTA and plasma clearance of iohexol were sufficiently accurate to measure GFR (moderately strong evidence). Renal clearance of DTPA, renal clearance of iohexol, and plasma clearance of inulin had sufficient accuracy (limited evidence). Endogenous creatinine clearance was an inaccurate method (strong evidence), as was plasma clearance of DTPA (limited evidence). The evidence to determine the accuracy of plasma iothalamate clearance was insufficient. With the exception of plasma clearance of inulin, only renal clearance methods had P30 > 90%. Limitations The included studies were few and most were old and small, which may limit generalizability. Requirements for sufficient accuracy may depend on clinical setting. At least moderately strong evidence suggests that renal clearance of 51Cr-EDTA or iothalamate and plasma clearance of 51Cr-EDTA or iohexol are sufficiently accurate methods to measure GFR.
|
|
