{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:26:12Z","timestamp":1774592772334,"version":"3.50.1"},"reference-count":25,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1998,1]]},"abstract":"<jats:p>OBJECTIVE: To determine the prevalence and biochemical characteristics of certain alleles of alpha 1-proteinase inhibitor in black and white South African patients with two common types of pathology causing the nephrotic syndrome. DESIGN: A cross sectional study of black and white patients with focal glomerulosclerosis (FGS) or minimal change disease (MCNS) and black and white controls. SETTING: The patients were drawn from the Paediatric Nephrology Units at the Johannesburg and Baragwanath Hospitals and the controls were drawn from the South African Blood Transfusion Service and the Paediatric Nephrology Clinic in Johannesburg. RESULTS: There was a significant increase in the prevalence of the V allele in black patients with FGS (12%) as compared to black controls (1%) (p = 0.01). None of the white patients with FGS had the V allele but two out the five coloured (mixed race) patients had the V allele (20%). An increase in the prevalence of the S allele of alpha 1PI was found in white patients with FGS and MCNS (10%) as compared to white controls (2%). The plasma elastase inhibitory capacity (EIC) associated with the phenotypes (PI) M1 (Ala213)S, M1 (Ala213) V, and M1 (Ala213) M1 (Ala213) was significantly decreased as compared to the EIC associated with PI M1 (Val213) M1 (Val213) (p = 0.006, p = 0.004, and p = 0.025, respectively). Twelve of 13 patients with FGS and infected with tuberculosis had either the M1 (Ala213) V or F alleles and required transplantation owing to the severity of the disease. All of these patients were either black or coloured. However, eight of 12 patients with FGS who had the M1 (Ala213) V or S alleles but were PPD negative did not require transplantation. CONCLUSION: It is possible that the combination of functionally less efficient alpha 1PI and an inflammatory challenge associated with an infection such as tuberculosis could predispose black and coloured nephrotic patients to more aggressive scarring in FGS.<\/jats:p>","DOI":"10.1136\/jmg.35.1.6","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"6-9","source":"Crossref","is-referenced-by-count":8,"title":["Variants of alpha 1-proteinase inhibitor in black and white South African patients with focal glomerulosclerosis and minimal change nephrotic syndrome."],"prefix":"10.1136","volume":"35","author":[{"given":"A C","family":"Halkas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M C","family":"Gaillard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P D","family":"Thomson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S L","family":"Green","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Ludewick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U","family":"Kala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1998,1,1]]},"reference":[{"key":"ref_1","first-page":"6","article-title":"Molecular basis of alpha-l-antitrypsin deficiency","volume":"84","author":"Brantly, M.; Nukiwa, T.; Crystal, R.G.","year":"1988","unstructured":"Brantly M, Nukiwa T, Crystal RG. Molecular basis of alpha-l-antitrypsin deficiency. Am J Med 1988;84(suppl 6A): 13-31.","journal-title":"Am J Med"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1164\/ajrccm\/145.6.1311","article-title":"Alpha-iprotease inhibitor in bronchial asthma: phenotypes and biochemical characteristics","volume":"145","author":"Gaillard, M.C.; Kilroe-Smith, T.A.; Nogueira, C.","year":"1992","unstructured":"Gaillard MC, Kilroe-Smith TA, Nogueira C, et al. Alpha-iprotease inhibitor in bronchial asthma: phenotypes and biochemical characteristics. Am Rev Respir Dis 1992;145: 1311-15.","journal-title":"Am Rev Respir Dis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/j.1399-0004.1994.tb04008.x","article-title":"Ethnic differences in the occurrence of the M1 (Ala2'13) haplotype of alpha-lantitrypsin in asthmatic and non-asthmatic black and white South Africans","volume":"45","author":"Gaillard, M.C.; Zwi, S.; Nogueira, C.M.","year":"1994","unstructured":"Gaillard MC, Zwi S, Nogueira CM, et al. Ethnic differences in the occurrence of the M1 (Ala2'13) haplotype of alpha-lantitrypsin in asthmatic and non-asthmatic black and white South Africans. Clin Genet 1994;45:122-7.","journal-title":"Clin Genet"},{"key":"ref_4","first-page":"765","article-title":"HLA antigens and atopic features in steroid response nephrotic syndrome of childhood","volume":"ii:","author":"Thomson, P.D.; Barratt, T.M.; Stokes, C.R.; Turner, M.W.; Soothill, J.F.","year":"1976","unstructured":"Thomson PD, Barratt TM, Stokes CR, Turner MW, Soothill JF. HLA antigens and atopic features in steroid response nephrotic syndrome of childhood. Lancet 1976;ii: 765-8.","journal-title":"Lancet"},{"key":"ref_5","first-page":"49","article-title":"Extracellular matrix remodelling by metalloproteinases and plasminogen activators","volume":"47","author":"Mignatti, P.","year":"1995","unstructured":"Mignatti P. Extracellular matrix remodelling by metalloproteinases and plasminogen activators. Kidney Int 1995; 47(suppl 49):S12-14.","journal-title":"Kidney Int"},{"key":"ref_6","first-page":"313","article-title":"Limited cleavage of human immunoglobulins by elastase of human neutrophil polymorphonuclear granulocytes. Possible modular of immune complex disease","volume":"39","author":"Folds, J.D.; Prince, I.J.; Spitznagel, J.K.","year":"1978","unstructured":"Folds JD, Prince IJ, Spitznagel JK. Limited cleavage of human immunoglobulins by elastase of human neutrophil polymorphonuclear granulocytes. Possible modular of immune complex disease. Lab Invest 1978;39:313-21.","journal-title":"Lab Invest"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1007\/BF00858986","article-title":"Balance between matrix synthesis and degradation: a determinant of glomerulosclerosis","volume":"9","author":"Schnaper, H.W.","year":"1995","unstructured":"Schnaper HW. Balance between matrix synthesis and degradation: a determinant of glomerulosclerosis. Pediatr Nephrol 1995;9:104-1 1.","journal-title":"Pediatr Nephrol"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/ki.1992.103","article-title":"Proteinases and glomerular matrix turnover","volume":"41","author":"Davies, M.; Martin, J.; Thomas, G.; Lovett, D.","year":"1992","unstructured":"Davies M, Martin J, Thomas G, Lovett D. Proteinases and glomerular matrix turnover. Kidney Int 1992;41:671-8.","journal-title":"Kidney Int"},{"key":"ref_9","first-page":"71","article-title":"Membranoproliferative glomerulonephritis and a, antitrypsin deficiency in children","volume":"88","author":"Strife, C.F.; Hug, G.; Chuck, G.; McAdams, A.J.; Davis, C.A.; Kline, J.J.","year":"1983","unstructured":"Strife CF, Hug G, Chuck G, McAdams AJ, Davis CA, Kline JJ. Membranoproliferative glomerulonephritis and a,antitrypsin deficiency in children. Pediatrics 1983;88:71-5.","journal-title":"Pediatrics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/BF00329135","article-title":"A new procedure for the determination of transferrinc (TFc) subtype by isoelectric focusing. Existence of two additional alleles, TTc4 and TT6","volume":"55","author":"Constans, J.; Kiihnl, P.; Vian, M.; Spietmann, W.","year":"1980","unstructured":"Constans J, Kiihnl P, Vian M, Spietmann W. A new procedure for the determination of transferrinc (TFc) subtype by isoelectric focusing. Existence of two additional alleles, TTc4 and TT6. Hum Genet 1980;55:111-14.","journal-title":"Hum Genet"},{"key":"ref_11","first-page":"1","article-title":"Rapid efficient DNA extraction for PCR from cells or blood","volume":"2","author":"Higushi, R.","year":"1989","unstructured":"Higushi R. Rapid efficient DNA extraction for PCR from cells or blood. Amplifications 1989;2:1-12.","journal-title":"Amplifications"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0009-9120(79)80137-X","article-title":"Comparison of specific protein assays in biological fluids by radial immunodiffusion and laser nephelometer","volume":"12","author":"Shulman, G.","year":"1979","unstructured":"Shulman G. Comparison of specific protein assays in biological fluids by radial immunodiffusion and laser nephelometer. Clin Biochem 1979;12:123-5.","journal-title":"Clin Biochem"},{"key":"ref_13","first-page":"167","article-title":"Determination of functional activity of a,-protease inhibitor and a, macroglobulin in human plasma using elastase","volume":"25","author":"Gaillard, M.C.; Kilroe-Smith, T.A.","year":"1987","unstructured":"Gaillard MC, Kilroe-Smith TA. Determination of functional activity of a,-protease inhibitor and a,macroglobulin in human plasma using elastase. J7 Clin Chem Clin Biochem 1987;25: 167-72.","journal-title":"J7 Clin Chem Clin Biochem"},{"key":"ref_14","first-page":"979","article-title":"Nephrotic syndrome of childhood at Baragwanath hospital - a 5 year analysis","volume":"30","author":"Jacobs, D.; Kala, U.; Milner, L.S.; Ninin, D.; Murray, J.","year":"1986","unstructured":"Jacobs D, Kala U, Milner LS, Ninin D, Murray J. Nephrotic syndrome of childhood at Baragwanath hospital - a 5 year analysis. Kidney Int 1986;30:979.","journal-title":"Kidney Int"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1007\/BF00857548","article-title":"Impact of tuberculosis in children with idiopathic nephrotic syndrome","volume":"7","author":"Kala, U.; Milner, L.S.; Jacobs, D.; Thomson, P.D.","year":"1993","unstructured":"Kala U, Milner LS, Jacobs D, Thomson PD. Impact of tuberculosis in children with idiopathic nephrotic syndrome. Pediatr Nephrol 1993;7:392-5.","journal-title":"Pediatr Nephrol"},{"key":"ref_16","first-page":"393","article-title":"Racial differences in the incidence and renal outcome of idiopathic focal segmental glomerulosclerosis in children","volume":"5","author":"Ingulli, E.; Tejani, A.","year":"1991","unstructured":"Ingulli E, Tejani A. Racial differences in the incidence and renal outcome of idiopathic focal segmental glomerulosclerosis in children. PediatrNephrol 1991;5:393-7.","journal-title":"PediatrNephrol"},{"key":"ref_17","first-page":"162936","article-title":"Anti-inflammatory properties of hepatic acute phase proteins: preferential induction of interleukin 1 (IL-1) receptor antagonist over IL-1 13 synthesis by human peripheral blood mononuclear cells. J7 Exp Med","volume":"178","author":"Tilg, H.; Vannier, E.; Vachino, G.; Dinarello, C.A.; Mier, J.W.","year":"1993","unstructured":"Tilg H, Vannier E, Vachino G, Dinarello CA, Mier JW. Anti-inflammatory properties of hepatic acute phase proteins: preferential induction of interleukin 1 (IL-1) receptor antagonist over IL-1 13 synthesis by human peripheral blood mononuclear cells. J7 Exp Med 1993;178:162936."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1165\/ajrcmb\/9.6.666","article-title":"Human a,-proteinase inhibitor binds to extracellular matrix in vivo","volume":"9","author":"Rinehart, A.R.; Mallya, S.; Simon, SR","year":"1993","unstructured":"Rinehart AR, Mallya S, Simon SR. Human a,-proteinase inhibitor binds to extracellular matrix in vivo. Am Jf Respir Cell Mol Biol 1993;9:666-79.","journal-title":"Am Jf Respir Cell Mol Biol"},{"key":"ref_19","first-page":"118","article-title":"Plasma levels and urinary excretion of fibrinolytic and protease inhibitory proteins in nephrotic syndrome","volume":"124","author":"Vaziri, N.D.; Gonzales, E.C.; Shayestehfar, B.; Barton, C.H.","year":"1994","unstructured":"Vaziri ND, Gonzales EC, Shayestehfar B, Barton CH. Plasma levels and urinary excretion of fibrinolytic and protease inhibitory proteins in nephrotic syndrome. J Lab Clin Med 1994;124:118-24.","journal-title":"J Lab Clin Med"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1378\/chest.103.3.812","article-title":"Variants of a,-antitrypsin in Puerto Rican children with asthma","volume":"103","author":"Colp, C.; Pappas, J.; Moran, D.; Lieberman, J.","year":"1993","unstructured":"Colp C, Pappas J, Moran D, Lieberman J. Variants of a,-antitrypsin in Puerto Rican children with asthma. Chest 1993;103:812-15.","journal-title":"Chest"},{"key":"ref_21","first-page":"2409","article-title":"Antitrypsin deficiency","volume-title":"molecular basis of inherited diseases. Vol 2","author":"a, Cox D.W.","year":"1995","unstructured":"Cox DW. a, Antitrypsin deficiency. In: Scriver CR, Baudet AL, Sly WS, Valle D, eds. Metabolic and molecular basis of inherited diseases. Vol 2. New York: McGraw-Hill, 1995: 2409-37."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/BF00865458","article-title":"Lymphocyte subpopulations, interleukin-2 and interleukin-2-receptor expression in childhood nephrotic syndrome","volume":"8","author":"Hulton, S.; Shah, V.; Byrne, M.; Morgan, G.; Barrat, T.M.; Dillon, M.J.","year":"1994","unstructured":"Hulton S, Shah V, Byrne M, Morgan G, Barrat TM, Dillon, MJ. Lymphocyte subpopulations, interleukin-2 and interleukin-2-receptor expression in childhood nephrotic syndrome. Pediatr Nephrol 1994;8: 135-9.","journal-title":"Pediatr Nephrol"},{"key":"ref_23","first-page":"681","article-title":"The effect ofa,-antitrypsin on the proliferative response of human peripheral blood lymphocytes","volume":"130","author":"Breit, S.N.; Luckhurst, E.; Penny, R.","year":"1983","unstructured":"Breit SN, Luckhurst E, Penny R. The effect ofa,-antitrypsin on the proliferative response of human peripheral blood lymphocytes. J1mmunol 1983;130:681-6."},{"key":"ref_24","first-page":"508","article-title":"Renal problems in black South African children","volume":"11","author":"Thomson, P.D.","year":"1997","unstructured":"Thomson PD. Renal problems in black South African children. PediatrNephrol 1997;11:508-12.","journal-title":"PediatrNephrol"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1172\/JCI115654","article-title":"Plasma levels of elastase specific fibrinopeptides correlate with proteinase inhibitor phenotype","volume":"89","author":"Weitz, J.I.; Silverman, K.; Thong, B.; Campbell, E.J.","year":"1992","unstructured":"Weitz JI, Silverman K, Thong B, Campbell EJ. Plasma levels of elastase specific fibrinopeptides correlate with proteinase inhibitor phenotype. _T Clin Invest 1992;89:766-73.","journal-title":"_T Clin Invest"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.35.1.6","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T19:40:16Z","timestamp":1760730016000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.35.1.6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,1]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[1998,1,1]]},"published-print":{"date-parts":[[1998,1]]}},"alternative-id":["10.1136\/jmg.35.1.6"],"URL":"https:\/\/doi.org\/10.1136\/jmg.35.1.6","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,1]]}}}