CD36单核苷酸多态性与2型糖尿病中医证型及血小板功能的研究
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摘要
目的
观察CD36基因单核苷酸多态性（SNPs）与汉族人群2型糖尿病中医证型及血小板功能的相关性，以及在糖尿病合并动脉粥样硬化性脑梗死的人群中是否存在变异，探讨糖尿病合并脑梗死的遗传学机制。
方法
研究一选择405名2型糖尿病患者，分为阴虚热盛、湿热困脾、气阴两虚伴血瘀、阴阳两虚四种证型，对照组选择与病例组性别、年龄匹配无糖尿病体检者539例。所有入组者检测空腹血糖、HbA1c、血脂、血小板计数，并采用聚合酶链反应—连接酶检测反应（PCR-LDR）技术检测CD36rs3211842、rs1761667两个位点的个体基因型。ELISA法测定血浆血栓素B2（TXB2）。
研究二选择107例气阴两虚伴血瘀糖尿病患者并伴有动脉粥样硬化性脑梗死，设为病例组，另设单纯动脉粥样硬化性脑梗死恢复期患者同类证型267例，列为对照组，检测方法和指标同研究一。
研究三选择107例糖尿病伴脑梗死患者，为病例组，另设单纯糖尿病无并发症患者298例，为对照组，检测方法和指标同研究一。
结果
研究一结果显示：糖尿病病例组及各辨证分型组CD36rs3211842、rs1761667基因型频率与对照组相比无统计学差异（P＞0.05）。气阴两虚伴血瘀组患者与对照组相比血小板计数、TXB2水平有统计学差异（P＜0.05）。
研究二结果发现气阴两虚型伴血瘀型糖尿病伴脑梗死组血糖、HbA1c、LDL、HDL与对照组相比，有显著性差异（P＜0.05）。CD36rs3211842基因型频率、等位基因频率与无糖尿病的脑梗死患者相比明显增高(X~2=6.358，P=0.043)，多元回归分析发现基因型AG+AA能够显著增加2型糖尿病并发脑梗死的发病风险（OR=2.460，95%CI=1.197~5.054，P=0.014），并与CH、LDL、TXB2水平呈正相关（P＜0.05）。CD36rs1761667基因型及等位基因频率两组间无显著性差异（P＞0.05）。
研究三结果发现病例组CD36rs1761667基因型频率分布与对照组相比无统计学差异（P>0.05），但等位基因频率与对照组相比有统计学差异（P=0.017），CD36rs3211842AG型基因频率及A等位基因频率分布显著高于对照组，两组间具有统计学差异(P=0.047，P=0.011)。多元logistic逐步回归分析提示rs3211842基因型AG+AA是2型糖尿病并发脑梗死的危险因素之一，并与TXB2升高有关（P＜0.05）。
结论
CD36基因rs3211842、rs1761667的变异可能与糖尿病及其中医证型无关，气阴两虚伴血瘀型患者血小板功能异常，表现在血小板计数升高，TXB2水平升高。CD36rs3211842AG+AA基因型可能是汉族人群2型糖尿病并发脑梗死的危险因素之一，与气阴两虚伴血瘀型糖尿病并发脑梗死相关，而CD36rs1761667位点可能与汉族人群2型糖尿病并发脑梗死无关，CD36rs3211842AG+AA基因型可能与血小板活化有关。
Objective： To explore the relationship between CD36single nucleotidepolymorphisms and TCM syndrome type of diabetes.
Methods: Study1:405patients with diabetes which were divided into four groups:extreme heat with yin asthenia type, wet and heat puzzling the spleen type, Qi and Yindeficiency with blood stasis type and Yin-Yang deficiency type. The control group selectednon-diabetes physical examination person539cases. Two loci of CD36rs3211842,rs1761667individual genotypes were detected using polymerase chain reaction-ligasedetection reaction (PCR-LDR). Enzyme linked immunosorbent assay (ELISA) was usedfor determination of plasma thromboxane B2(TXB2).
Study2: This study included107patients of Qi and Yin deficiency with blood stasistype diabetes accompany with atherosclerotic cerebral infarction.267patients withatherosclerotic cerebral infarction of the same TCM syndrome type is the control group.The methods is the same of study1.
Study3: This study included107patients of diabetes accompany with atheroscleroticcerebral infarction.298patients with diabetes is the control group. The methods is thesame of study1.
Results：Study1: There were no significant differences in the rs3211842andrs1761667genotype frequencies and allele frequencies between the four groups andcontrols（P＞0.05）. The platelet counts and plasma TXB2levels is significant differencesbetween of Qi and Yin deficiency with blood stasis type and controls（P＜0.05）.
Study2: The distribution of rs3211842genotype frequencies and allele frequenciesin the Qi and Yin deficiency with blood stasis type of diabetes with significant differences compare to the atherosclerotic cerebral infarction control (X2=6.358, P=0.043).Compared to GG, genotype AG+AA can increase the risk of diabetes with atheroscleroticcerebral infarction after multi-factor logistic analysis and stepwise regression analysis（OR=2.460，95%CI=1.197~5.054，P=0.014）. The GAgenotype in combination withAAgenotype showed a significant association with HDL, CH, TXB2(P＜0.05).
Study3: The distribution of rs3211842AG genotype frequencies and A allelefrequencies in diabetes with atherosclerotic cerebral infarction was significant differencescompare to the diabetes control (P=0.047，P=0.011). The AG genotype in combinationwith AA genotype showed a significant association with TXB2level(P＜0.05) and increasethe risk of diabetes with atherosclerotic cerebral infarction after stepwise regressionanalysis(P＜0.05).
Conclusions：CD36rs3211842, rs1761667is not associated with diabetes and TCMsyndrome type of diabetes in our cohort. CD36rs3211842is the independent risk factors ofdiabetes with atherosclerotic cerebral infarction. CD36SNPs have correlation with plateletfunction.
观察CD36基因单核苷酸多态性（SNPs）与汉族人群2型糖尿病中医证型及血小板功能的相关性，以及在糖尿病合并动脉粥样硬化性脑梗死的人群中是否存在变异，探讨糖尿病合并脑梗死的遗传学机制。
方法
研究一选择405名2型糖尿病患者，分为阴虚热盛、湿热困脾、气阴两虚伴血瘀、阴阳两虚四种证型，对照组选择与病例组性别、年龄匹配无糖尿病体检者539例。所有入组者检测空腹血糖、HbA1c、血脂、血小板计数，并采用聚合酶链反应—连接酶检测反应（PCR-LDR）技术检测CD36rs3211842、rs1761667两个位点的个体基因型。ELISA法测定血浆血栓素B2（TXB2）。
研究二选择107例气阴两虚伴血瘀糖尿病患者并伴有动脉粥样硬化性脑梗死，设为病例组，另设单纯动脉粥样硬化性脑梗死恢复期患者同类证型267例，列为对照组，检测方法和指标同研究一。
研究三选择107例糖尿病伴脑梗死患者，为病例组，另设单纯糖尿病无并发症患者298例，为对照组，检测方法和指标同研究一。
结果
研究一结果显示：糖尿病病例组及各辨证分型组CD36rs3211842、rs1761667基因型频率与对照组相比无统计学差异（P＞0.05）。气阴两虚伴血瘀组患者与对照组相比血小板计数、TXB2水平有统计学差异（P＜0.05）。
研究二结果发现气阴两虚型伴血瘀型糖尿病伴脑梗死组血糖、HbA1c、LDL、HDL与对照组相比，有显著性差异（P＜0.05）。CD36rs3211842基因型频率、等位基因频率与无糖尿病的脑梗死患者相比明显增高(X~2=6.358，P=0.043)，多元回归分析发现基因型AG+AA能够显著增加2型糖尿病并发脑梗死的发病风险（OR=2.460，95%CI=1.197~5.054，P=0.014），并与CH、LDL、TXB2水平呈正相关（P＜0.05）。CD36rs1761667基因型及等位基因频率两组间无显著性差异（P＞0.05）。
研究三结果发现病例组CD36rs1761667基因型频率分布与对照组相比无统计学差异（P>0.05），但等位基因频率与对照组相比有统计学差异（P=0.017），CD36rs3211842AG型基因频率及A等位基因频率分布显著高于对照组，两组间具有统计学差异(P=0.047，P=0.011)。多元logistic逐步回归分析提示rs3211842基因型AG+AA是2型糖尿病并发脑梗死的危险因素之一，并与TXB2升高有关（P＜0.05）。
结论
CD36基因rs3211842、rs1761667的变异可能与糖尿病及其中医证型无关，气阴两虚伴血瘀型患者血小板功能异常，表现在血小板计数升高，TXB2水平升高。CD36rs3211842AG+AA基因型可能是汉族人群2型糖尿病并发脑梗死的危险因素之一，与气阴两虚伴血瘀型糖尿病并发脑梗死相关，而CD36rs1761667位点可能与汉族人群2型糖尿病并发脑梗死无关，CD36rs3211842AG+AA基因型可能与血小板活化有关。
Objective： To explore the relationship between CD36single nucleotidepolymorphisms and TCM syndrome type of diabetes.
Methods: Study1:405patients with diabetes which were divided into four groups:extreme heat with yin asthenia type, wet and heat puzzling the spleen type, Qi and Yindeficiency with blood stasis type and Yin-Yang deficiency type. The control group selectednon-diabetes physical examination person539cases. Two loci of CD36rs3211842,rs1761667individual genotypes were detected using polymerase chain reaction-ligasedetection reaction (PCR-LDR). Enzyme linked immunosorbent assay (ELISA) was usedfor determination of plasma thromboxane B2(TXB2).
Study2: This study included107patients of Qi and Yin deficiency with blood stasistype diabetes accompany with atherosclerotic cerebral infarction.267patients withatherosclerotic cerebral infarction of the same TCM syndrome type is the control group.The methods is the same of study1.
Study3: This study included107patients of diabetes accompany with atheroscleroticcerebral infarction.298patients with diabetes is the control group. The methods is thesame of study1.
Results：Study1: There were no significant differences in the rs3211842andrs1761667genotype frequencies and allele frequencies between the four groups andcontrols（P＞0.05）. The platelet counts and plasma TXB2levels is significant differencesbetween of Qi and Yin deficiency with blood stasis type and controls（P＜0.05）.
Study2: The distribution of rs3211842genotype frequencies and allele frequenciesin the Qi and Yin deficiency with blood stasis type of diabetes with significant differences compare to the atherosclerotic cerebral infarction control (X2=6.358, P=0.043).Compared to GG, genotype AG+AA can increase the risk of diabetes with atheroscleroticcerebral infarction after multi-factor logistic analysis and stepwise regression analysis（OR=2.460，95%CI=1.197~5.054，P=0.014）. The GAgenotype in combination withAAgenotype showed a significant association with HDL, CH, TXB2(P＜0.05).
Study3: The distribution of rs3211842AG genotype frequencies and A allelefrequencies in diabetes with atherosclerotic cerebral infarction was significant differencescompare to the diabetes control (P=0.047，P=0.011). The AG genotype in combinationwith AA genotype showed a significant association with TXB2level(P＜0.05) and increasethe risk of diabetes with atherosclerotic cerebral infarction after stepwise regressionanalysis(P＜0.05).
Conclusions：CD36rs3211842, rs1761667is not associated with diabetes and TCMsyndrome type of diabetes in our cohort. CD36rs3211842is the independent risk factors ofdiabetes with atherosclerotic cerebral infarction. CD36SNPs have correlation with plateletfunction.
引文
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