{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:54:06Z","timestamp":1788537246981,"version":"build-2803163510"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objective\u2014<\/jats:title>\n                    <jats:p>\n                      This post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial) assessed the individual variation in total homocysteine (tHcy)\u2013lowering response after an average 4.5 years of 0.8 mg daily folic acid therapy in Chinese hypertensive adults and evaluated effect modification by methylenetetrahydrofolate reductase (\n                      <jats:italic>MTHFR<\/jats:italic>\n                      ) C677T genotypes and serum folate levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results\u2014<\/jats:title>\n                    <jats:p>\n                      This analysis included 16\u2009413 participants from the CSPPT, who were randomly assigned to 2 double-blind treatment groups: either 10-mg enalapril+0.8-mg folic acid or 10-mg enalapril, daily and had individual measurements of serum folate and tHcy levels at baseline and exit visits and\n                      <jats:italic>MTHFR<\/jats:italic>\n                      C677T genotypes. Mean baseline tHcy levels were comparable between the 2 treatment groups (14.5\u00b18.5 versus 14.4\u00b18.1 \u03bcmol\/L;\n                      <jats:italic>P<\/jats:italic>\n                      =0.561). After 4.5 years of treatment, mean tHcy levels were reduced to 12.7\u00b16.1 \u03bcmol\/L in the enalapril+folic acid group, but almost stayed the same in the enalapril group (14.4\u00b17.9 \u03bcmol\/L, group difference: 1.61 \u03bcmol\/L; 11% reduction). More importantly, tHcy lowering varied by\n                      <jats:italic>MTHFR<\/jats:italic>\n                      genotypes and serum folate levels. Compared with CC and CT genotypes, participants with the TT genotype had a more prominent L-shaped curve between tHcy and serum folate levels and required higher folate levels (at least 15 ng\/mL) to eliminate the differences in tHcy by genotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>\n                      Compared with CC or CT, tHcy in the TT group manifested a heightened L-shaped curve from low to high folate levels, but this difference in tHcy by genotype was eliminated when plasma folate levels reach \u224815 ng\/mL or higher. Our data raised the prospect to tailor folic acid therapy according to individual\n                      <jats:italic>MTHFR<\/jats:italic>\n                      C677T genotype and folate status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      . Unique identifier: NCT00794885.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.117.310211","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T05:00:13Z","timestamp":1516856413000},"page":"679-685","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["<i>MTHFR<\/i>\n                    Gene and Serum Folate Interaction on Serum Homocysteine Lowering"],"prefix":"10.1161","volume":"38","author":[{"given":"Xiao","family":"Huang","sequence":"first","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhui","family":"Qin","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Yang","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lishun","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongfei","family":"Jiang","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianglin","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanqun","family":"Jiang","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Bao","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Su","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingli","family":"He","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Song","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhao","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. 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Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. 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Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Li","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renqang","family":"Yang","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Wu","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Hong","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinhua","family":"Wu","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. 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Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binyan","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. 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Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan Fan","family":"Hou","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. Wang, B.W., F.F.H.); Institute of Biomedicine, Anhui Medical University, Hefei, China (W.Y., S.J.); China Agricultural University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Huo","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China (X.H., H.B., H.S., P.L., R.Y., Y. Wu, K.H., Q.W., X.C.); National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.Q., C.J., X.Z., Y.S., Y. 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