PubMed:10084598 JSONTXT

{"project":"PubTator4TogoVar","denotations":[{"id":"10084598_0","span":{"begin":34,"end":39},"obj":"ProteinMutation"},{"id":"10084598_1","span":{"begin":321,"end":326},"obj":"ProteinMutation"},{"id":"10084598_2","span":{"begin":370,"end":375},"obj":"ProteinMutation"},{"id":"10084598_3","span":{"begin":525,"end":529},"obj":"ProteinMutation"},{"id":"10084598_4","span":{"begin":681,"end":685},"obj":"ProteinMutation"},{"id":"10084598_5","span":{"begin":800,"end":804},"obj":"ProteinMutation"},{"id":"10084598_6","span":{"begin":805,"end":809},"obj":"ProteinMutation"},{"id":"10084598_7","span":{"begin":826,"end":830},"obj":"ProteinMutation"},{"id":"10084598_8","span":{"begin":831,"end":835},"obj":"ProteinMutation"},{"id":"10084598_9","span":{"begin":1006,"end":1010},"obj":"ProteinMutation"},{"id":"10084598_10","span":{"begin":1011,"end":1015},"obj":"ProteinMutation"},{"id":"10084598_11","span":{"begin":1117,"end":1121},"obj":"ProteinMutation"},{"id":"10084598_12","span":{"begin":1122,"end":1126},"obj":"ProteinMutation"},{"id":"10084598_13","span":{"begin":1128,"end":1132},"obj":"ProteinMutation"},{"id":"10084598_14","span":{"begin":1133,"end":1137},"obj":"ProteinMutation"},{"id":"10084598_15","span":{"begin":1143,"end":1147},"obj":"ProteinMutation"},{"id":"10084598_16","span":{"begin":1148,"end":1152},"obj":"ProteinMutation"},{"id":"10084598_17","span":{"begin":1376,"end":1380},"obj":"ProteinMutation"},{"id":"10084598_18","span":{"begin":1381,"end":1385},"obj":"ProteinMutation"},{"id":"10084598_19","span":{"begin":1390,"end":1394},"obj":"ProteinMutation"},{"id":"10084598_20","span":{"begin":1395,"end":1399},"obj":"ProteinMutation"},{"id":"10084598_21","span":{"begin":1414,"end":1418},"obj":"ProteinMutation"},{"id":"10084598_22","span":{"begin":1419,"end":1423},"obj":"ProteinMutation"},{"id":"10084598_23","span":{"begin":1471,"end":1475},"obj":"ProteinMutation"},{"id":"10084598_24","span":{"begin":1476,"end":1480},"obj":"ProteinMutation"},{"id":"10084598_25","span":{"begin":1539,"end":1543},"obj":"ProteinMutation"},{"id":"10084598_26","span":{"begin":1544,"end":1548},"obj":"ProteinMutation"},{"id":"10084598_27","span":{"begin":1601,"end":1606},"obj":"ProteinMutation"},{"id":"10084598_28","span":{"begin":1771,"end":1776},"obj":"ProteinMutation"}],"attributes":[{"id":"10084598_0_ProteinMutation","pred":"proteinmutation","subj":"10084598_0","obj":"rs137853240"},{"id":"10084598_1_ProteinMutation","pred":"proteinmutation","subj":"10084598_1","obj":"rs137853240"},{"id":"10084598_2_ProteinMutation","pred":"proteinmutation","subj":"10084598_2","obj":"rs137853240"},{"id":"10084598_3_ProteinMutation","pred":"proteinmutation","subj":"10084598_3","obj":"rs137853240"},{"id":"10084598_4_ProteinMutation","pred":"proteinmutation","subj":"10084598_4","obj":"rs137853240"},{"id":"10084598_5_ProteinMutation","pred":"proteinmutation","subj":"10084598_5","obj":"rs137853240"},{"id":"10084598_6_ProteinMutation","pred":"proteinmutation","subj":"10084598_6","obj":"rs137853240"},{"id":"10084598_7_ProteinMutation","pred":"proteinmutation","subj":"10084598_7","obj":"rs137853240"},{"id":"10084598_8_ProteinMutation","pred":"proteinmutation","subj":"10084598_8","obj":"rs137853240"},{"id":"10084598_9_ProteinMutation","pred":"proteinmutation","subj":"10084598_9","obj":"rs137853240"},{"id":"10084598_10_ProteinMutation","pred":"proteinmutation","subj":"10084598_10","obj":"rs137853240"},{"id":"10084598_11_ProteinMutation","pred":"proteinmutation","subj":"10084598_11","obj":"rs137853240"},{"id":"10084598_12_ProteinMutation","pred":"proteinmutation","subj":"10084598_12","obj":"rs137853240"},{"id":"10084598_13_ProteinMutation","pred":"proteinmutation","subj":"10084598_13","obj":"rs137853240"},{"id":"10084598_14_ProteinMutation","pred":"proteinmutation","subj":"10084598_14","obj":"rs137853240"},{"id":"10084598_15_ProteinMutation","pred":"proteinmutation","subj":"10084598_15","obj":"rs137853240"},{"id":"10084598_16_ProteinMutation","pred":"proteinmutation","subj":"10084598_16","obj":"rs137853240"},{"id":"10084598_17_ProteinMutation","pred":"proteinmutation","subj":"10084598_17","obj":"rs137853240"},{"id":"10084598_18_ProteinMutation","pred":"proteinmutation","subj":"10084598_18","obj":"rs137853240"},{"id":"10084598_19_ProteinMutation","pred":"proteinmutation","subj":"10084598_19","obj":"rs137853240"},{"id":"10084598_20_ProteinMutation","pred":"proteinmutation","subj":"10084598_20","obj":"rs137853240"},{"id":"10084598_21_ProteinMutation","pred":"proteinmutation","subj":"10084598_21","obj":"rs137853240"},{"id":"10084598_22_ProteinMutation","pred":"proteinmutation","subj":"10084598_22","obj":"rs137853240"},{"id":"10084598_23_ProteinMutation","pred":"proteinmutation","subj":"10084598_23","obj":"rs137853240"},{"id":"10084598_24_ProteinMutation","pred":"proteinmutation","subj":"10084598_24","obj":"rs137853240"},{"id":"10084598_25_ProteinMutation","pred":"proteinmutation","subj":"10084598_25","obj":"rs137853240"},{"id":"10084598_26_ProteinMutation","pred":"proteinmutation","subj":"10084598_26","obj":"rs137853240"},{"id":"10084598_27_ProteinMutation","pred":"proteinmutation","subj":"10084598_27","obj":"rs137853240"},{"id":"10084598_28_ProteinMutation","pred":"proteinmutation","subj":"10084598_28","obj":"rs137853240"}],"text":"The hepatic nuclear factor-1alpha G319S variant is associated with early-onset type 2 diabetes in Canadian Oji-Cree.\nMutations in the gene encoding hepatic nuclear factor-1alpha (HNF-1alpha) have been found in patients with maturity-onset diabetes of the young. We identified a new variant in the HNF-1alpha gene, namely G319S, in Ontario Oji-Cree with type 2 diabetes. G319S is within the proline II-rich domain of the trans-activation site of HNF-1alpha and alters a glycine residue that is conserved throughout evolution. S319 was absent from 990 alleles taken from subjects representing six other ethnic groups, suggesting that it is private for Oji-Cree. We found that 1) the S319 allele was significantly more prevalent in diabetic than nondiabetic Oji-Cree (0.209 vs. 0.087; P = 0.000001); 2) S319/S319 homozygotes and S319/G319 heterozygotes, respectively, had odds ratios for type 2 diabetes of 4.00 (95% confidence interval, 2.65-6.03) and 1.97 (95% confidence interval, 1.44-2.70) compared with G319/G319 homozygotes; 3) there was a significant difference in the mean age of onset of type 2 diabetes, with G319/G319, S319/G319, and S319/S319 subjects affected in the fifth, fourth, and third decades of life, respectively. In subjects with type 2 diabetes, we also found significantly lower body mass index and significantly higher post-challenge plasma glucose in S319/S319 and S319/G319 compared with G319/G319 subjects. Finally, among nondiabetic subjects, S319/G319 heterozygotes had significantly lower plasma insulin than G319/G319 homozygotes. The presence of the private HNF-1alpha G319S variant in a large number of Oji-Cree with type 2 diabetes and its strong association with type 2 diabetes susceptibility are unique among human populations. Also, G319S is associated with a distinct form of type 2 diabetes, characterized by onset at an earlier age, lower body mass, and a higher postchallenge plasma glucose."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":224,"end":260},"obj":"HP_0004904"}],"text":"The hepatic nuclear factor-1alpha G319S variant is associated with early-onset type 2 diabetes in Canadian Oji-Cree.\nMutations in the gene encoding hepatic nuclear factor-1alpha (HNF-1alpha) have been found in patients with maturity-onset diabetes of the young. We identified a new variant in the HNF-1alpha gene, namely G319S, in Ontario Oji-Cree with type 2 diabetes. G319S is within the proline II-rich domain of the trans-activation site of HNF-1alpha and alters a glycine residue that is conserved throughout evolution. S319 was absent from 990 alleles taken from subjects representing six other ethnic groups, suggesting that it is private for Oji-Cree. We found that 1) the S319 allele was significantly more prevalent in diabetic than nondiabetic Oji-Cree (0.209 vs. 0.087; P = 0.000001); 2) S319/S319 homozygotes and S319/G319 heterozygotes, respectively, had odds ratios for type 2 diabetes of 4.00 (95% confidence interval, 2.65-6.03) and 1.97 (95% confidence interval, 1.44-2.70) compared with G319/G319 homozygotes; 3) there was a significant difference in the mean age of onset of type 2 diabetes, with G319/G319, S319/G319, and S319/S319 subjects affected in the fifth, fourth, and third decades of life, respectively. In subjects with type 2 diabetes, we also found significantly lower body mass index and significantly higher post-challenge plasma glucose in S319/S319 and S319/G319 compared with G319/G319 subjects. Finally, among nondiabetic subjects, S319/G319 heterozygotes had significantly lower plasma insulin than G319/G319 homozygotes. The presence of the private HNF-1alpha G319S variant in a large number of Oji-Cree with type 2 diabetes and its strong association with type 2 diabetes susceptibility are unique among human populations. Also, G319S is associated with a distinct form of type 2 diabetes, characterized by onset at an earlier age, lower body mass, and a higher postchallenge plasma glucose."}