苏北农村地区高血压人群肾功能流行病学研究
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摘要
慢性肾脏疾病(chronic kidney disease, CKD)发病率在全世界范围内呈明显升高趋势，已成为21世纪全人类面临的主要公共健康问题之一。CKD进展至终末期肾衰（end stage renal disease, ESRD）需依赖肾脏替代治疗而生存，不仅影响患者的生存质量，而且给患者及社会带来沉重的负担。如何更好的防治CKD、延缓肾功能衰退已成为目前研究的热点。
原发性高血压是最常见的心血管疾病，也是慢性肾脏病重要的危险因素之一。我国人群高血压患病率高，平均每10个成人中就有2人患高血压，估计目前全国至少有2亿高血压患者，并且仍呈增长态势。因此，在高血压患者中发现早期肾功能减退的患者并针对相关危险因素进行早期干预具有十分重要的临床意义。
心血管疾病(cardiac vascular disease, CVD)是CKD患者最严重的并发症和首要死亡原因。近年来，血浆同型半胱氨酸（homocysteine, Hcy）升高作为动脉粥样硬化新的危险因素被广泛关注。国内外已有大量证据表明，Hcy与许多疾病的发生发展有密切联系，是CVD的独立危险因子。
此外，Hcy还与脑卒中神经变性疾病、神经管缺陷以及终末期肾脏病的联系密切。目前，CKD和终末期肾脏病患者的高Hcy现象已经得到临床研究者的普遍认同，高Hcy被认为是CKD患者CVD风险显著增高的重要原因之一。
肾功能受损可以引起血浆Hcy水平升高，而在非CKD的一般人群中，血浆Hcy水平也与肾功能呈负相关。虽然高同型半胱氨酸血症在人类肾功能不全的发病中是否起作用尚不清楚，但在动物实验中高同型半胱氨酸血症可能诱导肾损伤。
亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase, MTHFR）是催化5,10-亚甲基四氢叶酸转化为5-甲基四氢叶酸的关键酶，而5-甲基四氢叶酸是Hcy再甲基化为蛋氨酸反应过程中的甲基供体，MTHFR基因677位点C>T的遗传变异是导致血浆Hcy水平的升高重要的原因之一。然而，很少有研究关注MTHFR C677T基因多态性和肾功能之间的关系。
我们从2008年底开始在江苏省连云港市赣榆县和东海县部分乡镇开展一项“原发性高血压人群脑卒中一级预防的随机临床试验”，对赣榆、东海两县部分乡镇居民进行了肾功能、血浆Hcy水平和MTHFR C677T基因多态性的检测，通过横断面分析了解在苏北农村地区大样本高血压人群中肾功能的分布情况，研究影响肾功能分布的因素，重点关注Hcy、MTHFR C677T基因多态性和高血压患者肾功能的关系，为上述问题提供我国大规模人群的数据，以期在高血压人群中发现影响肾功能的相关危险因素，为CKD患者的临床早期干预提供科学依据。
第一部分苏北农村地区高血压人群肾功能分布及其影响因素研究
背景：慢性肾脏病（chronic kidney disease, CKD）在全世界范围内的发病率明显升高，而高血压是慢性肾脏病非常重要的危险因素，因此，发现高血压人群中早期肾功能减退的危险因素并予以干预具有十分重要的临床意义。目的：通过横断面分析，了解在苏北农村地区大样本高血压人群中肾功能的分布情况，并研究影响肾功能分布的因素。
方法：本研究人群来自国家Ⅰ类新药马来酸依那普利叶酸片多中心随机对照Ⅳ期临床试验中国脑卒中一级预防研究中江苏省连云港农村社区原发性高血压患者的基线资料，其中共纳入18814例45~75岁筛选期的原发性高血压患者，进行问卷调查、人体测量和血样采集，测定肾功能、血糖、血脂和同型半胱氨酸等相关指标。
结果：本研究人群共计18814例原发性高血压患者，以肾小球滤过率（estimatedglomerular filtration rate，eGFR）<60ml/min/1.73m2作为划分CKD的界值，CKD的患病率是3.3%，其中，男性和女性的患病率分别是3.1%和3.4%。男性和女性患者eGFR水平均随着年龄增加而减低。随着Hcy水平的增加，男性和女性患者eGFR水平均降低。多元线性回归分析显示，在男性和女性患者中，年龄、体质指数（BMI）、Hcy、舒张压（DBP）、血糖和血脂与eGFR呈显著负相关，收缩压（SBP）与eGFR水平呈显著正相关。多元Logistic回归分析显示，在男性患者中，年龄和Hcy水平每增加1个单位，CKD的风险分别增加10%（OR：1.10，95%CI：1.07-1.13，P<0.001）和2%（OR：1.02，95%CI：1.01-1.03，P<0.001）；在女性患者中，年龄和Hcy水平每增加1个单位，CKD的风险分别增加7%（OR：1.07，95%CI：1.05-1.09，P<0.001）和6%（OR：1.06，95%CI：1.04-1.08，P<0.001）。
结论：本研究发现，我国连云港农村社区的原发性高血压人群中CKD的患病率为3.3%，年龄和Hcy水平是影响高血压患者肾功能的重要因素。
第二部分苏北农村地区高血压人群MTHFR C677T基因多态性与肾功能的分子流行病学研究
背景：血浆同型半胱氨酸（homocysteine, Hcy）水平和肾功能呈负相关。在终末期肾病中，严重肾功能损害将不可避免地导致高同型半胱氨酸血症。但是，高同型半胱氨酸血症在人类肾功能不全的发病中是否起作用尚不清楚，近期有研究提示，Hcy是CKD的独立预测因素。
目的：通过横断面分析，研究苏北农村地区原发性高血压人群中Hcy和Hcy代谢关键酶亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase, MTHFR）C677T基因多态性与肾功能的关联性。
方法：本研究人群来自国家Ⅰ类新药马来酸依那普利叶酸片多中心随机对照Ⅳ期临床试验中国脑卒中一级预防研究中江苏省连云港农村社区原发性高血压患者的基线资料，其中共纳入18814例45~75岁筛选期的原发性高血压患者，进行问卷调查、人体测量和血样采集，测定肾功能、血糖、血脂、同型半胱氨酸水平和MTHFR C677T基因多态性等相关指标。
结果：本研究发现研究人群MTHFR C677T基因型和eGFR水平之间的关系具有性别差异，在男性患者中，TT基因型的患者较CC基因型的患者eGFR水平显著下降1.37ml/min/1.73m（2P=0.004）。将eGFR进行五等分和二等分后，Logistic回归分析显示，校正年龄、BMI、收缩压和舒张压之后，TT基因型的男性患者处于低水平eGFR的风险更高，其OR值分别为1.32（95%CI:1.08-10.62,P=0.007）和1.25(95%CI:1.11-1.41, P=0.0003)。以eGFR<60ml/min/1.73m2作为划分CKD的标准，在男性和女性患者中，均未发现MTHFR C677T基因型与CKD发生风险有显著性关联（P>0.05）。
结论：本研究结果表明，在苏北农村地区男性高血压患者中，MTHFR C677T基因多态性和肾功能之间存在相关性，TT基因型eGFR水平显著下降，提示MTHFRC677T遗传变异有可能参与了CKD的病理过程，可能是CKD的易感位点。
Prevalence of chronic kidney disease (CKD) is increasing dramaticallyworldwide, which is one of the dominant public health problems to all of humanity inthe21stcentury. CKD will progress into end stage renal disease (ESRD) requiringrenal replacement therapy. This will not only influence life quality of CKD patientsseriously, but also bring heavy economic burden to patients and the society. How toprevent and treat CKD in order to prolong the decline of renal function is becoming aresearch hot point at present。
Primary hypertension is the commonest cardiac vascular disease (CVD), andalso one of the most important risk factor for CKD. Hypertension is highly prevalentin China. It is estimated that there are at least200million hypertensives now, two outof every10people. For this reason, figuring out patitents with impared renal functionin hypertensive patients and intervening with the relevant risk factors are meaningfullfor the early prevention of CKD.
CVD is the most serious comorbidity and the primary cause of deaths for CKDpatients. In recent years, more and more attention has been paid to homocysteine(Hcy), a new risk factor for atherosclerosis. Increasing evidences demonstrated thatHcy was associated with risks for stroke, coronary heart disease and a number ofother disease statuses such as neural tube defect and also ESRD.Hyperhomocysteinemia in CKD and ESRD patients is generally acknowledged andhas been taken as an important reason for the high CVD morbidity in CKD patients.
Significant loss of renal function will inevitably lead to hyperhomocysteinemia,as frequently observed in patients with ESRD. However, plasma level of Hcy is alsonegatively correlated with renal function in general polulation. It is not clear whether hyperhomocysteinemia plays a pathogenic role in decreased renal function in humans,but some researchers found in animal models that hyperhomocysteinemia couldinduce glomerular injury.
Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of5,10-methylenetetrahydrofolate to5-methyltetrahydrofolate, a co-substrate forhomocysteine remethylation to methionine. C677T, a single nucleotide polymorphism(C>T) at nucleotide position677, leads to Ala>Val codon substitution at amino acidposition222. MTHFR C677T is a major genetic determinant forhyperhomocysteinemia. However, few have investigated the association betweenC677T and kidney function.
From2008, we carried out a clinical research,“China Stroke Primary PreventStudy”, in rural residents, aged45~75years, who lived in the villages in Ganyu andDonghai Counties of Lianyungang District. we examined the renal function, plasmaHcy levels and MTHFR C677T polymorphism, in order to investigate the distributionof renal function in a large population of primary hypertensives in North Jiangsu andfigure out the risk factors for early renal function decline, focusing on the relationshipamong Hcy, MTHFR C677T polymorphism and renal function. We are expecting thatthe data in a large hypertensive population can provide clues for the questions aboveand also providing scientific basis for early prevention of CKD according to thecontrol of associated risk factors.
Part1The Distribution and Impact Factors of Renal Function inHypertensive Population of Rural Communities in NorthJiangsu
Background:
The incidence of chronic kidney disease (CKD) is increasing worldwide. Hypertension is one of the most important risk factor of CKD. So it is meaningful toinvestigate and figure out the impact factors for early renal function decline inhypertensive patients. Pretreating these risk factors will be very important for theprevention of CKD in hypertensive patients.
Objective:To investigate the distribution of renal function in a large hypertensive patients innorth Jiangsu of China and figure the impact factors for early renal function decline ina cross-sectional study.Methods:We analyzed the baseline data of participants of an ongoing China Stroke PrimaryPrevention Trial (CSPPT): a Post-marketing, Double-blind, Randomized ControlledTrial in Lianyungang, Jiangsu province. A total of18,814primary hypertensivepatients (6914males,11900females) were included in the study.
Results:The percentage of subjects with CKD (eGFR<60ml/min/1.73m2) was3.3%, whichwere3.1%and3.4%respectively in males and females. According to multiple linearregression analysis, the glomerular filtration rate estimated from serum creatininelevels (eGFR) were positively correlated with age, homocysteine (Hcy), diastolicblood pressure (DBP), fasting blood glucose (FBG) and total cholesterol (TC), andinversely correlated with systolic blood pressure (SBP). When dividing subjects intoCKD and non-CKD, in males, older age and higher Hcy level were associated with ahigher risk for CKD, with (OR=1.10,95%CI:1.07-1.13, P<0.00and OR=1.02,95%CI:1.01-1.03, P=0.00); similarly in females, the ORs were1.07(95%CI:1.05-1.09, P<0.00) and1.06(95%CI:1.04-1.08, P<0.00).
Conclusion:The percentage of subjects with CKD (eGFR<60ml/min/1.73m2) in primaryhypertensive patients is3.3%, which is higher than general people in China. Age andHcy level are the most important factors associated with renal function.
Part2Molecular Epidemiology Study on the association ofMethylenetetrahydrofolate reductase C677T polymorphismwith Renal Function in Hypertensive Population of RuralCommunities in North Jiangsu
Background:Plasma level of total homocysteine (Hcy) is negatively correlated with kidneyfunction in general population. However, the causal mechanism of this correlation ispoorly understood.
Objective:The purpose of this study is to investigate the association ofmethylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, which isa major genetic determinant of the plasma tHcy level, with estimated glomerularfiltration rate (eGFR) in Chinese of north Jiangsu.Methods:We analyzed the baseline data of participants of an ongoing China Stroke PrimaryPrevention Trial (CSPPT): a Post-marketing, Double-blind, Randomized ControlledTrial in Lianyungang, Jiangsu province. A total of18814primary hypertensivepatients (6914males,11900females) were included in the study.
Results:Association between the eGFR and MTHFR C677T genotype was examined bysex-specific regression analyses. In males, TT genotype was associated with1.37ml/min/1.73m2decrease in eGFR (p=0.004) and with an increased risk (OR=1.32,p=0.008) for the lowest quintile of eGFR after adjusting for age, BMI, and bloodpressures. However, such association was not observed in females (p>0.05). Thisassociation suggests MTHFR C677T polymorphism may play a role in the regulation of eGFR in males.
Conclusion:MTHFR C677T is a risk factor for decreasing kidney function in Chinese males ofnorth Jiangsu, implicating this gene in the pathogenesis of chronic kidney disease(CKD).
原发性高血压是最常见的心血管疾病，也是慢性肾脏病重要的危险因素之一。我国人群高血压患病率高，平均每10个成人中就有2人患高血压，估计目前全国至少有2亿高血压患者，并且仍呈增长态势。因此，在高血压患者中发现早期肾功能减退的患者并针对相关危险因素进行早期干预具有十分重要的临床意义。
心血管疾病(cardiac vascular disease, CVD)是CKD患者最严重的并发症和首要死亡原因。近年来，血浆同型半胱氨酸（homocysteine, Hcy）升高作为动脉粥样硬化新的危险因素被广泛关注。国内外已有大量证据表明，Hcy与许多疾病的发生发展有密切联系，是CVD的独立危险因子。
此外，Hcy还与脑卒中神经变性疾病、神经管缺陷以及终末期肾脏病的联系密切。目前，CKD和终末期肾脏病患者的高Hcy现象已经得到临床研究者的普遍认同，高Hcy被认为是CKD患者CVD风险显著增高的重要原因之一。
肾功能受损可以引起血浆Hcy水平升高，而在非CKD的一般人群中，血浆Hcy水平也与肾功能呈负相关。虽然高同型半胱氨酸血症在人类肾功能不全的发病中是否起作用尚不清楚，但在动物实验中高同型半胱氨酸血症可能诱导肾损伤。
亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase, MTHFR）是催化5,10-亚甲基四氢叶酸转化为5-甲基四氢叶酸的关键酶，而5-甲基四氢叶酸是Hcy再甲基化为蛋氨酸反应过程中的甲基供体，MTHFR基因677位点C>T的遗传变异是导致血浆Hcy水平的升高重要的原因之一。然而，很少有研究关注MTHFR C677T基因多态性和肾功能之间的关系。
我们从2008年底开始在江苏省连云港市赣榆县和东海县部分乡镇开展一项“原发性高血压人群脑卒中一级预防的随机临床试验”，对赣榆、东海两县部分乡镇居民进行了肾功能、血浆Hcy水平和MTHFR C677T基因多态性的检测，通过横断面分析了解在苏北农村地区大样本高血压人群中肾功能的分布情况，研究影响肾功能分布的因素，重点关注Hcy、MTHFR C677T基因多态性和高血压患者肾功能的关系，为上述问题提供我国大规模人群的数据，以期在高血压人群中发现影响肾功能的相关危险因素，为CKD患者的临床早期干预提供科学依据。
第一部分苏北农村地区高血压人群肾功能分布及其影响因素研究
背景：慢性肾脏病（chronic kidney disease, CKD）在全世界范围内的发病率明显升高，而高血压是慢性肾脏病非常重要的危险因素，因此，发现高血压人群中早期肾功能减退的危险因素并予以干预具有十分重要的临床意义。目的：通过横断面分析，了解在苏北农村地区大样本高血压人群中肾功能的分布情况，并研究影响肾功能分布的因素。
方法：本研究人群来自国家Ⅰ类新药马来酸依那普利叶酸片多中心随机对照Ⅳ期临床试验中国脑卒中一级预防研究中江苏省连云港农村社区原发性高血压患者的基线资料，其中共纳入18814例45~75岁筛选期的原发性高血压患者，进行问卷调查、人体测量和血样采集，测定肾功能、血糖、血脂和同型半胱氨酸等相关指标。
结果：本研究人群共计18814例原发性高血压患者，以肾小球滤过率（estimatedglomerular filtration rate，eGFR）<60ml/min/1.73m2作为划分CKD的界值，CKD的患病率是3.3%，其中，男性和女性的患病率分别是3.1%和3.4%。男性和女性患者eGFR水平均随着年龄增加而减低。随着Hcy水平的增加，男性和女性患者eGFR水平均降低。多元线性回归分析显示，在男性和女性患者中，年龄、体质指数（BMI）、Hcy、舒张压（DBP）、血糖和血脂与eGFR呈显著负相关，收缩压（SBP）与eGFR水平呈显著正相关。多元Logistic回归分析显示，在男性患者中，年龄和Hcy水平每增加1个单位，CKD的风险分别增加10%（OR：1.10，95%CI：1.07-1.13，P<0.001）和2%（OR：1.02，95%CI：1.01-1.03，P<0.001）；在女性患者中，年龄和Hcy水平每增加1个单位，CKD的风险分别增加7%（OR：1.07，95%CI：1.05-1.09，P<0.001）和6%（OR：1.06，95%CI：1.04-1.08，P<0.001）。
结论：本研究发现，我国连云港农村社区的原发性高血压人群中CKD的患病率为3.3%，年龄和Hcy水平是影响高血压患者肾功能的重要因素。
第二部分苏北农村地区高血压人群MTHFR C677T基因多态性与肾功能的分子流行病学研究
背景：血浆同型半胱氨酸（homocysteine, Hcy）水平和肾功能呈负相关。在终末期肾病中，严重肾功能损害将不可避免地导致高同型半胱氨酸血症。但是，高同型半胱氨酸血症在人类肾功能不全的发病中是否起作用尚不清楚，近期有研究提示，Hcy是CKD的独立预测因素。
目的：通过横断面分析，研究苏北农村地区原发性高血压人群中Hcy和Hcy代谢关键酶亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase, MTHFR）C677T基因多态性与肾功能的关联性。
方法：本研究人群来自国家Ⅰ类新药马来酸依那普利叶酸片多中心随机对照Ⅳ期临床试验中国脑卒中一级预防研究中江苏省连云港农村社区原发性高血压患者的基线资料，其中共纳入18814例45~75岁筛选期的原发性高血压患者，进行问卷调查、人体测量和血样采集，测定肾功能、血糖、血脂、同型半胱氨酸水平和MTHFR C677T基因多态性等相关指标。
结果：本研究发现研究人群MTHFR C677T基因型和eGFR水平之间的关系具有性别差异，在男性患者中，TT基因型的患者较CC基因型的患者eGFR水平显著下降1.37ml/min/1.73m（2P=0.004）。将eGFR进行五等分和二等分后，Logistic回归分析显示，校正年龄、BMI、收缩压和舒张压之后，TT基因型的男性患者处于低水平eGFR的风险更高，其OR值分别为1.32（95%CI:1.08-10.62,P=0.007）和1.25(95%CI:1.11-1.41, P=0.0003)。以eGFR<60ml/min/1.73m2作为划分CKD的标准，在男性和女性患者中，均未发现MTHFR C677T基因型与CKD发生风险有显著性关联（P>0.05）。
结论：本研究结果表明，在苏北农村地区男性高血压患者中，MTHFR C677T基因多态性和肾功能之间存在相关性，TT基因型eGFR水平显著下降，提示MTHFRC677T遗传变异有可能参与了CKD的病理过程，可能是CKD的易感位点。
Prevalence of chronic kidney disease (CKD) is increasing dramaticallyworldwide, which is one of the dominant public health problems to all of humanity inthe21stcentury. CKD will progress into end stage renal disease (ESRD) requiringrenal replacement therapy. This will not only influence life quality of CKD patientsseriously, but also bring heavy economic burden to patients and the society. How toprevent and treat CKD in order to prolong the decline of renal function is becoming aresearch hot point at present。
Primary hypertension is the commonest cardiac vascular disease (CVD), andalso one of the most important risk factor for CKD. Hypertension is highly prevalentin China. It is estimated that there are at least200million hypertensives now, two outof every10people. For this reason, figuring out patitents with impared renal functionin hypertensive patients and intervening with the relevant risk factors are meaningfullfor the early prevention of CKD.
CVD is the most serious comorbidity and the primary cause of deaths for CKDpatients. In recent years, more and more attention has been paid to homocysteine(Hcy), a new risk factor for atherosclerosis. Increasing evidences demonstrated thatHcy was associated with risks for stroke, coronary heart disease and a number ofother disease statuses such as neural tube defect and also ESRD.Hyperhomocysteinemia in CKD and ESRD patients is generally acknowledged andhas been taken as an important reason for the high CVD morbidity in CKD patients.
Significant loss of renal function will inevitably lead to hyperhomocysteinemia,as frequently observed in patients with ESRD. However, plasma level of Hcy is alsonegatively correlated with renal function in general polulation. It is not clear whether hyperhomocysteinemia plays a pathogenic role in decreased renal function in humans,but some researchers found in animal models that hyperhomocysteinemia couldinduce glomerular injury.
Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of5,10-methylenetetrahydrofolate to5-methyltetrahydrofolate, a co-substrate forhomocysteine remethylation to methionine. C677T, a single nucleotide polymorphism(C>T) at nucleotide position677, leads to Ala>Val codon substitution at amino acidposition222. MTHFR C677T is a major genetic determinant forhyperhomocysteinemia. However, few have investigated the association betweenC677T and kidney function.
From2008, we carried out a clinical research,“China Stroke Primary PreventStudy”, in rural residents, aged45~75years, who lived in the villages in Ganyu andDonghai Counties of Lianyungang District. we examined the renal function, plasmaHcy levels and MTHFR C677T polymorphism, in order to investigate the distributionof renal function in a large population of primary hypertensives in North Jiangsu andfigure out the risk factors for early renal function decline, focusing on the relationshipamong Hcy, MTHFR C677T polymorphism and renal function. We are expecting thatthe data in a large hypertensive population can provide clues for the questions aboveand also providing scientific basis for early prevention of CKD according to thecontrol of associated risk factors.
Part1The Distribution and Impact Factors of Renal Function inHypertensive Population of Rural Communities in NorthJiangsu
Background:
The incidence of chronic kidney disease (CKD) is increasing worldwide. Hypertension is one of the most important risk factor of CKD. So it is meaningful toinvestigate and figure out the impact factors for early renal function decline inhypertensive patients. Pretreating these risk factors will be very important for theprevention of CKD in hypertensive patients.
Objective:To investigate the distribution of renal function in a large hypertensive patients innorth Jiangsu of China and figure the impact factors for early renal function decline ina cross-sectional study.Methods:We analyzed the baseline data of participants of an ongoing China Stroke PrimaryPrevention Trial (CSPPT): a Post-marketing, Double-blind, Randomized ControlledTrial in Lianyungang, Jiangsu province. A total of18,814primary hypertensivepatients (6914males,11900females) were included in the study.
Results:The percentage of subjects with CKD (eGFR<60ml/min/1.73m2) was3.3%, whichwere3.1%and3.4%respectively in males and females. According to multiple linearregression analysis, the glomerular filtration rate estimated from serum creatininelevels (eGFR) were positively correlated with age, homocysteine (Hcy), diastolicblood pressure (DBP), fasting blood glucose (FBG) and total cholesterol (TC), andinversely correlated with systolic blood pressure (SBP). When dividing subjects intoCKD and non-CKD, in males, older age and higher Hcy level were associated with ahigher risk for CKD, with (OR=1.10,95%CI:1.07-1.13, P<0.00and OR=1.02,95%CI:1.01-1.03, P=0.00); similarly in females, the ORs were1.07(95%CI:1.05-1.09, P<0.00) and1.06(95%CI:1.04-1.08, P<0.00).
Conclusion:The percentage of subjects with CKD (eGFR<60ml/min/1.73m2) in primaryhypertensive patients is3.3%, which is higher than general people in China. Age andHcy level are the most important factors associated with renal function.
Part2Molecular Epidemiology Study on the association ofMethylenetetrahydrofolate reductase C677T polymorphismwith Renal Function in Hypertensive Population of RuralCommunities in North Jiangsu
Background:Plasma level of total homocysteine (Hcy) is negatively correlated with kidneyfunction in general population. However, the causal mechanism of this correlation ispoorly understood.
Objective:The purpose of this study is to investigate the association ofmethylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, which isa major genetic determinant of the plasma tHcy level, with estimated glomerularfiltration rate (eGFR) in Chinese of north Jiangsu.Methods:We analyzed the baseline data of participants of an ongoing China Stroke PrimaryPrevention Trial (CSPPT): a Post-marketing, Double-blind, Randomized ControlledTrial in Lianyungang, Jiangsu province. A total of18814primary hypertensivepatients (6914males,11900females) were included in the study.
Results:Association between the eGFR and MTHFR C677T genotype was examined bysex-specific regression analyses. In males, TT genotype was associated with1.37ml/min/1.73m2decrease in eGFR (p=0.004) and with an increased risk (OR=1.32,p=0.008) for the lowest quintile of eGFR after adjusting for age, BMI, and bloodpressures. However, such association was not observed in females (p>0.05). Thisassociation suggests MTHFR C677T polymorphism may play a role in the regulation of eGFR in males.
Conclusion:MTHFR C677T is a risk factor for decreasing kidney function in Chinese males ofnorth Jiangsu, implicating this gene in the pathogenesis of chronic kidney disease(CKD).
引文
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