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We sought to recapitulate this association between Hp genotype and DN in mice genetically modified at the Hp locus. We assessed morphometric, histologic, and functional parameters involved in the development and progression of DN in mice with diabetes mellitus (DM) with either the Hp 2-2 or Hp 1-1 genotype. Morphometric analysis demonstrated that glomerular and proximal tubular hypertrophy were significantly increased in Hp 2-2 DM mice. Histological analysis demonstrated that Hp 2-2 DM mice had significantly more collagen type IV, smooth muscle actin, and increased renal iron deposition. Studies of renal function demonstrated creatinine clearance time and albuminuria were increased in Hp 2-2 DM mice. Vitamin E provided significant protection against the development of functional and histological features characteristic of DN to Hp 2-2 DM but not to Hp 1-1 DM mice. These studies serve to strengthen the association between the Hp 2-2 genotype and diabetic renal disease and suggest a pharmacogenomic interaction may exist between the Hp genotype and vitamin E.<\/jats:p>","DOI":"10.1152\/ajprenal.90655.2008","type":"journal-article","created":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T02:09:13Z","timestamp":1233194953000},"page":"F830-F838","source":"Crossref","is-referenced-by-count":18,"title":["Pharmacogenomic effect of vitamin E on kidney structure and function in transgenic mice with the haptoglobin 2-2 genotype and diabetes mellitus"],"prefix":"10.1152","volume":"296","author":[{"given":"Farid M.","family":"Nakhoul","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Miller-Lotan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoda","family":"Awad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rabea","family":"Asleh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kheir","family":"Jad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nakhoul","family":"Nakhoul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy","family":"Asaf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niroz","family":"Abu-Saleh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew P.","family":"Levy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000076889.23082.F1"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000156653.05853.b9"},{"key":"R3","unstructured":"Awadallah S, Hamad M.The prevalence of type II diabetes mellitus is haptoglobin phenotype-independent.Cytobios101: 145\u2013150, 2000."},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1258\/000456303770367298"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2007.02.033"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.8.842"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199401063300103"},{"key":"R8","unstructured":"Bowman BH, Kurosky A.Haptoglobin: the evolutionary product of duplication, unequal crossing over, and point mutation.Adv Hum Genet12: 189\u2013261, 1982."},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1159\/000078408"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.1995.tb00422.x"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1042\/cs0960221"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1159\/000098563"},{"key":"R13","unstructured":"Costacou T, Ferrell RE, Orchard T.Haptoglobin genotype and renal disease progression in type I diabetes (Abstract).Diabetologia51: 5473\u20135474, 2007."},{"key":"R14","doi-asserted-by":"crossref","unstructured":"Dunn SR, Qi Z, Bottinger EP, Breyer MD, Sharma K.Utility of endogenous creatinine clearance as a measure of renal function in mice.Kidney Int65: 1959\u20131967, 1967.","DOI":"10.1111\/j.1523-1755.2004.00600.x"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1046\/j.0742-3071.2001.00574.x"},{"key":"R16","doi-asserted-by":"crossref","unstructured":"Gburek J, Verroust PJ, Willnow TE, Fyfe JC, Nowacki W, Jacobsen C, Moestrup SK, Christiansen EI.Megalin and cubulin are endocytotic receptors involved in renal clearance of hemoglobin.J Am Soc Nephrol13: 423\u2013430, 2002.","DOI":"10.1681\/ASN.V132423"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.717"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119853"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.47.5.821"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00232.x"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000133025.23732.46"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200009283431313"},{"key":"R23","unstructured":"Levy AP.Complication-resistant patients. 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