Haptoglobin gene polymorphism in type 2 diabetic patients with and without nephropathy: An Egyptian study

BACKGROUND: The development and progression of diabetic microvascular complications including nephropathy are related to the degree of glycemic control and oxidative stress and may be influenced by genetic factors. The aim of the present study was to investigate the association between haptoglobin (Hp) gene polymorphism and the occurrence of diabetic nephropathy in patients with type 2 diabetes mellitus and to find a possible link between Hp phenotypes and the inflammatory parameters; serum C-reactive protein (CRP), interleukin- 6 (IL-6), and Hp. METHODS: The study included 60 normotensive type 2 diabetic patients (>5 years duration) categorized into three equal groups (normo-, micro-, and macroalbuminuric), according to urinary albumin excretion (UAE). In addition, 20 age- and sex-matched individuals were selected to serve as a control group. Serum CRP, IL-6, and Hp concentrations were measured and Hp phenotyping was conducted using polyacrylamide gel electrophoresis. RESULTS: The frequency of Hp phenotype 1-1 (Hp 1-1) in diabetic patients with normoalbuminuria was 7/20 (35%) as compared with 1/20 (5%) in diabetics with macroalbuminuria (p=0.02). However, the frequency of Hp 2-2 was greater in diabetics with macroalbuminuria (12/20, 60%) than in those with normoalbuminuria or controls (5/20, 25%; p=0.03). Patients with diabetic nephropathy (micro- or macroalbuminuria) had higher levels of serum CRP, IL-6, and Hp than those without nephropathy (normoalbuminuria). Serum Hp levels in type 2 diabetics were higher in Hp phenotype 2-2 than in Hp 1-1; however, serum CRP and IL-6 levels did not differ significantly between Hp phenotype groups. Moreover, there were significant positive correlations between UAE and serum levels of CRP, IL-6, and Hp in diabetic patients. CONCLUSIONS: Hp phenotype 2-2 is considered to be a major susceptibility gene for the development of nephropathy in type 2 diabetic patients. In addition, the significant association between inflammatory parameters and UAE indicates that inflammation may be a pathogenic mechanism of renal injury in type 2 diabetics. Moreover, serum IL-6 and Hp may be good prognostic factors for the development of nephropathy in the course of diabetes mellitus. Future research on the use of anti-inflammatory therapy may result in a new approach to the treatment and prevention of diabetic nephropathy.     

白介素18基因型及血清水平与2型糖尿病肾病的相关性

目的研究白介素18（IL-18）基因型及血清水平与2型糖尿病肾病（DN）的关系。方法采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术,检测360例2型糖尿病患者（160例伴DN）及180名正常对照组的IL-18的基因多态性,同时采用酶联免疫吸附试验（ELISA）检测血清IL-18水平。结果与对照组比较,糖尿病肾病组血清IL-18水平显著高于对照组（P〈0．01）。IL-18基因-137G／C多态性在两组人群中的分布差异有统计学意义（P〈0．05）,携带-137C等位基因的糖尿病肾病患者血清IL-18水平显著高于不携带者（P〈0．05）。结论IL-18基因-137G／C多态性与DN的发病可能具有相关性,其中C等位基因可能是DN发病的遗传易感基因;携带C等位基因的个体可能通过促进IL-18的高度表达进而增加了DN的发病风险。     

Interleukin-6 polymorphism (-634C/G) in the promotor region and the progression of diabetic nephropathy in type 2 diabetes.

AIMS: Interleukin-6 (IL-6) is a multifunctional cytokine produced by many different cell types, including glomerular mesangial cells. Recently, a novel C/G polymorphism at position -634 in the promotor region of the IL-6 gene has been reported. The aim of this study was to investigate whether the -634C/G polymorphism is associated with an increased risk for progression to diabetic nephropathy as well as elevated levels of IL-6 secretion by peripheral blood mononuclear cells. METHODS: The frequency of the -634C/G polymorphism was determined in Japanese patients with Type 2 diabetes and either normoalbuminuria (n = 162), microalbuminuria (n = 138), or macroalbuminuria (n = 154) by polymerase chain reaction-restriction fragment length polymorphism analysis. The level of IL-6 secretion in relation to genotype was assessed in lipopolysaccharide or advanced glycation end products-stimulated IL-6 secretion by peripheral mononuclear cells. RESULTS: The frequency of the -634G/G genotype and -634*G allele was significantly increased in the patients with macroalbuminuria compared with patients with normoalbuminuria (genotype: chi2 = 6.787, Pc = 0.0368; allele: chi2 = 9.080, Pc = 0.0104). Stepwise multiple regression analysis in these patients showed that hypertension (F = 40.48) and IL-6-634 gene polymorphism (F = 5.48) were the relevant variables for the progression of Type 2 diabetic nephropathy. Analysis of the IL-6 secretion data revealed that individuals carrying the -634*G allele had a higher IL-6 secretion capacity than those without the *G allele (P < 0.05). CONCLUSIONS: These results suggest that the IL-6-634C/G polymorphism may be a possible genetic susceptibility factor for the progression of diabetic nephropathy.     

Association of C-reactive protein with coronary heart disease risk factors in patients with type 2 diabetes mellitus

The assessment of markers of systemic inflammation, such as C-reactive protein (CRP) and interleukin 6 (IL6), could be used to identify persons at high risk of coronary heart disease (CHD). This study evaluates the relationship of CRP and IL6 with CHD risk factors in patients with type 2 diabetes mellitus (DM) with CHD and age and sex matched type 2 DM controls without CHD. CRP, IL-6, total plasma homocysteine (tHcy), lipoprotein (a) [Lp(a)] and sialic acid (SA) were determined in 55 type 2 diabetic patients with CHD and 51 age- and sex-matched type 2 diabetic controls without CHD. Multivariate and logistic regression analyses were used to relate these markers with CHD risk factors. CRP (P=0.02) and tHcy (P=0.03) were significantly higher in patients with CHD compared with the control group even after correction for age and sex. IL6, Lp(a), SA and lipid parameters were not significantly different between the two groups of patients. After adjustment for potential confounders, the odds ratio (OR) for elevated CRP was 2.00 (95% confidence interval [CI], 1.12-3.58) (P=0.02) but the OR for IL6 was 3.41 95% CI, 0.70-17.17 (P=0.14). Partial correlation analyses of CRP and IL6 with other variables showed significant correlation of CRP with tHcy, and SA in patients with CHD only. Our results support the inclusion of CRP (high-sensitivity assay), in the risk assessment of diabetic subjects.     

Interleukin-18 contributes more closely to the progression of diabetic nephropathy than other diabetic complications

Diabetic complication is comprised of a wide variety of pathophysiological factors involving proinflammatory cytokines, adipokines, and oxidative stress, among others. Each of these complications differs in their incidence and the stage of their occurrence. We examined cytokines and stress markers in 48 patients with type 2 diabetes mellitus and compared the difference of their contribution to pathogenesis between nephropathy and other diabetic complications. Hemoglobin A1c correlated with the level of low-density lipoprotein-cholesterol, and significantly elevated in the severe macroangiopathy group. Cystatin C increased in the severe microangiopathy groups but did not increase in the macroangiopathy group. The levels of interleukin 18 (IL-18), high-sensitive CRP (H-CRP), liver-type fatty acid binding protein, and 8-hydroxy-2-deoxyguanosine increased in the severe microangiopathy group. These data suggest the participation of proinflammatory signaling and oxidative stress in the progression of microangiopathy. In particular, IL-18 and H-CRP were significantly elevated only in the severe nephropathy group but did not significantly elevate in other complications. These data suggest another effect of IL-18 on glomerulus in addition to its proinflammatory effect. In conclusion, we propose that IL18 has a specific role that contributes more closely to the progression of diabetic nephropathy than other diabetic complications.     

Significant association of the interleukin-6 gene polymorphisms C-174G and A-598G with type 2 diabetes

Elevated blood concentrations of IL-6 have been shown to predict type 2 diabetes. Because the impact of IL-6 gene polymorphisms on diabetes status, parameters of the metabolic syndrome, and low-grade systemic inflammation has not been analyzed in a population-based study, we investigated the association of the IL-6 single nucleotide polymorphisms C-174G and A-598G on these parameters in 704 elderly participants of the Kooperative Gesundheitsforschung im Raum Augsburg/Cooperative Research in the Region of Augsburg (KORA) Survey 2000. Both -174G and -598G alleles were significantly associated with type 2 diabetes (-174G: odds ratio = 1.51, 95% confidence interval = 1.11-2.07, P = 0.0096; -598G: odds ratio = 1.56, 95% confidence interval = 1.13-2.15, P = 0.0069) but not with impaired glucose tolerance. In subgroup analyses, the association reached statistical significance in men and in leaner subjects (body mass index 相似文献   

亚甲基四氢叶酸还原酶基因多态性与糖尿病肾病相关性研究

目的：研究亚甲基四氢叶酸还原酶（MTHFR）基因多态性与2型糖尿病肾病的关系。方法：运用聚合酶链反应－限制性片段长度多态性技术（PCR－RFLP）检测85例2型糖尿病患者（其中39例伴糖尿病肾病）及57例正常对照组MTHFR C677T基因型,采用高效液相色谱法测定血浆同型半胱酸水平。结果：糖尿病肾病组MTHFR基因TT纯合基因型,CT杂合基因型及T等位基因频率（分别为38．21％,51．28％,53．85％）均明显高于糖尿病不伴肾病组（分别为19．57％,28．26％,33．70％）及正常对照组（分别为17．54％,28．07％,31．58）,基因型和等位基因频率分布差异均有统计学意义（P＜0．05）,而MTHFR基因该多态性在不伴肾病组与正常对照组之间差异无显著性（P＞0．05）,T等位基因与糖尿病肾病的发生密切相关（OR＝2．30,95％可信区间;1．24－4．26）。糖尿病肾病组,糖尿病不伴肾病组及正常对照组中,MTHFR基因有C677T突变者血浆同型半胱氨酸水平均显著高于无基因突变者。结论：MTHFR基因C677T位碱基突变致血浆同型半胱氨酸水平高是糖尿病肾病发病的重要遗传因素。     

Variations in association of Interleukin 6 -G174C single nucleotide polymorphism with type 2 diabetes mellitus—a review

Inflammation plays a role in the etiology of type 2 diabetes mellitus (DM). Interleukin-6 is one of the inflammatory markers which play role in the pathogenesis of diabetes mellitus DM. Single nucleotide polymorphism (SNP); -G174C in interleukin ?6 (IL-6) gene promoter area has been reported to be associated with type 2 DM (T2DM). The frequency of polymorphism is found to be variable in various ethnic groups and also within an ethnic group. Many studies reported a positive association between T2DM and IL-6 SNP although quite a number of other studies failed to find such association. IL-6 polymorphism has been found to be associated with higher serum IL-6 levels, insulin resistance and BMI, although these findings are also challenged by many studies. There is no single explanation for such highly variable results in different studies. Presence of yet unidentified gene polymorphism in linkage disequilibrium with IL-6 SNP could be responsible. The different results can also be attributed to the study groups differing as age, gender distribution, age of onset of disease, life style, degree of obesity and glucose tolerance. This review highlights the varying results reported in association of IL 6 –G174C SNP with risk of T2DM, serum IL-6 levels, BMI and insulin resistance.     

Tumor necrosis factor-alpha and Interleukin-10 gene promoter polymorphisms in Turkish rheumatoid arthritis patients

Tumor necrosis factor and interleukin 10 have been implicated in the pathogenesis of rheumatoid arthritis (RA). Certain single-nucleotide polymorphisms (SNPs) within the promoter region of the IL-10 and TNF genes have been associated with altered levels of circulating IL10 and TNF. We aimed to explore the association of IL-10 and TNF-alpha polymorphisms in Turkish RA patients. We analyzed the association of TNF-alpha (-308G/A, -238G/A, -376G/A) and IL10 (-1082G/A, -819C/T, -592C/A) polymorphisms in 98 Turkish patients with rheumatoid arthritis and 122 healthy subjects using ARMS-PCR. The correlation of these findings with RF positivity and erosive disease in RA patients was also sought. A significant association was found between having RA and -1082 G allele (p = 0.008; OR = 1.44, 95% CI 1.11-1.86). There was no association between RA and -819C/T polymorphism. Significant differences were observed in IL10 GCC and ACC haplotypes distribution between RA and control subjects (p = 0.006; OR = 1.46, 95% CI 1.13-1.89 and p = 0.011; OR = 1.43, 95% CI 1.09-1.88, respectively). No statistically significant association was found between TNF-alpha 308G/A, -238G/A, -376G/A polymorphisms and RA. No significant association was found between RF positivity and erosive disease and TNF-alpha, IL10 gene polymorphisms. In addition, when combined genotypes were analyzed, no significant difference was found between RA patients and healthy controls. Our findings suggest that IL-10 1082 G/A polymorphism or GCC, ACC haplotypes may be associated with RA in Turkish patients.     

The Role of Toll-Like Receptors in Diabetes-Induced Inflammation: Implications for Vascular Complications

Diabetes confers an increased risk for both microvascular and macrovascular complications. Numerous studies have reported increased levels of biomarkers of inflammation that could predispose to vascular complications. The pattern recognition receptors of the innate immune response, such as Toll-like receptors (TLRs), especially TLR2 and TLR4, have been incriminated in both atherosclerosis and insulin resistance. Studies have reported increased expression and activity of these receptors in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus. Most recently, knockout of TLR2 has been shown to attenuate the proinflammatory state of T1DM and the progression of diabetic nephropathy. The increased activity of TLRs in diabetes could be the result of a conspiracy of both endogenous and exogenous ligands. Biomediators of increased TLR2 and TLR4 activity include tumor necrosis factor-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1, and type 1 interferons. Modulating these TLRs could be beneficial in forestalling diabetic complications given the pivotal role of inflammation in both microvascular and macrovascular complications.     

Interleukin-6 (IL-6) –572C→G promoter polymorphism is associated with type 2 diabetes risk in Koreans

Objective  Increased levels of inflammatory markers, such as interleukin-6 ( IL -6), are associated with type 2 diabetes (T2DM). We investigated the association of IL-6 gene polymorphisms with T2DM and circulating levels of IL -6 in Koreans.
Subjects  A total of 1477 subjects with normal glucose tolerance and 476 T2DM patients were included.
Measurements  We examined IL-6 – 174G→C, –572C→G, –597G→A and –1363G→T promoter region polymorphisms. The main outcome measures were the odds ratio (OR) on T2DM risk and serum concentrations of IL -6 and high-sensitivity C-reactive protein (hs-CRP).
Results  Homozygosity for the rare G allele IL-6 – 572C→G was associated with a higher risk of T2DM [OR 1·69 (95%CI 1·11–2·58), P  = 0·015]. Serum IL -6 concentrations were associated with the IL-6 – 572C→G genotype in control subjects (G/G: 2·33 ± 0·41: C/G: 1·53 ± 0·09: C/C: 1·72 ± 0·08 ng/l, P  = 0·023). Also in the control group, subjects homozygous for the rare G allele showed significantly higher concentrations of hs-CRP than C/C and C/G carriers (G/G: 13·6 ± 2·9: C/G: 9·2 ± 0·6: C/C: 7·8 ± 0·4 mg/l, P  = 0·003). The C-allele at the IL-6 – 174 SNP was very rare (< 0·01) and –597G→A and –1363G→T were monomorphic in this population.
Conclusions  Our data demonstrate that the IL-6 – 572G/G genotype is associated with higher serum IL -6 and hs-CRP concentrations and with increased risk for T2DM.     

Putative role of polymorphisms in UCP1-3 genes for diabetic nephropathy

Increased production of reactive oxygen species (ROS) has been suggested as a cause of diabetic complications. Uncoupling proteins (UCPs) have been ascribed a role in reducing the formation of ROS, and genetic variation in genes encoding for UCPs could thus be putative candidate genes for diabetic nephropathy. To test this hypothesis we searched for association between the A-->G (-3862) variant in UCP1, the insertion/deletion (I/D) polymorphism in exon 8 in UCP2, and the C-->T (-55) polymorphism in UCP3 and diabetic nephropathy in 218 diabetic patients with normal urinary albumin excretion rate (AER), 216 with micro- or macroalbuminuria, and in 106 control subjects without a family history of diabetes. We did not find any association between the different polymorphisms and diabetic nephropathy, nor did we observe any difference in AER among carriers of different UCP1-3 genotypes. We could, however, confirm the reported association between BMI and the UCP3 -55 C-->T polymorphism; patients carrying the T allele had higher BMI than patients homozygous for the C allele (26.4+/-4.2 vs. 25.3+/-4.3 kg/m(2); P=.01). We conclude that studied polymorphisms in the UCP1-3 genes do not play a major role in the development of micro- or macroalbuminuria in Scandinavian diabetic patients.     

An IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in men infected with human immunodeficiency virus

Kaposi sarcoma (KS) is an angioproliferative inflammatory condition that occurs commonly in patients infected with human immunodeficiency virus (HIV). Inflammatory cytokines and growth factors promote the development of KS. Because physiologically important cytokine polymorphisms modulate host inflammatory responses, we investigated the association between KS and common regulatory polymorphisms in 5 proinflammatory cytokine genes encoding interleukin (IL) IL-1alpha, IL-1beta, tumor necrosis factor (TNF) alpha, TNF-beta, and IL-6 and in the IL-1 receptor antagonist (IL1RN). We also examined the contribution of stromal-derived factor 1 and chemokine receptor 5 (Delta32) polymorphisms to KS development. The population consisted of 115 HIV-infected men with KS and 126 deceased HIV-infected men without KS. The only strong association was observed between an IL6 promoter polymorphism (G-174C) and susceptibility to KS in HIV-infected men (P =.0035). Homozygotes for IL6 allele G, associated with increased IL6 production, were overrepresented among patients with KS (P =.0046), whereas allele C homozygotes were underrepresented (P =.0062). Substantial in vitro evidence indicates that IL-6 contributes to the pathogenesis of KS. Our results show that IL6 promoter genotypes associated with altered gene expression are risk factors for development of KS. Identification of a genetic risk factor for development of KS has important clinical implications for prevention and therapy.     

Interleukin-6-174 G > C polymorphism affects the association between IL-6 plasma levels and insulin resistance in type 2 diabetic patients

Interleukin-6 (IL-6), a powerful inflammatory mediator, plays a pivotal role in the pathogenesis of insulin resistance and type 2 diabetes. Recently, the IL-6 promoter polymorphism, at position -174 (G > C), has been associated to insulin sensitivity although contrasting data have been reported. The aim of this study was to evaluate the effect of the IL-6-174 G > C polymorphism on insulin resistance. In 238 type 2 diabetic patients without diabetic complications and in 255 control subjects, age and gender-matched, we evaluated the IL-6 -174 G > C genotype, the IL-6 plasma levels and the insulin resistance by the homeostasis model assessment (HOMA). The levels of IL-6 and HOMA were not genotype-dependent and were higher in diabetic patients (p < 0.01). Control subjects, both C+ (CG + CC genotypes) and C- (GG genotype) carriers, showed IL-6 plasma levels significantly related to BMI, fasting insulin and HOMA. The same relationships were found in C+ diabetic carriers. Differently, diabetic C- carriers did not show any relationship between IL-6 levels and all the evaluated variables. Interestingly, all the correlations were dependent on BMI. These findings highlight that IL-6-174 G > C polymorphism affects insulin resistance in type 2 diabetes, where C+ carriers have an insulin resistance "IL-6-sensitive", while C- carriers do not. The identification of two categories of diabetic patients may, therefore, lead to different therapeutic strategies in the management of insulin resistance.     

Analysis of the association between diabetic nephropathy and polymorphisms in the aldose reductase gene in Type 1 and Type 2 diabetes mellitus.

AIMS: To investigate the association between polymorphisms of the aldose reductase gene and diabetic nephropathy in both Type 1 and Type 2 diabetes mellitus, and to carry out a meta-analysis of published results. METHODS: We have investigated the role of two aldose reductase polymorphisms in four independent cohorts of cases and controls (two each with Type 1 and Type 2 diabetes) drawn from two ethnic populations, including 471 patients with nephropathy and 494 control diabetic patients without nephropathy. A C/T transition at position -106, and a (CA)n microsatellite marker 2.1 kb from the start site of the aldose reductase gene were genotyped in nephropathic patients and non-nephropathic controls from each cohort. RESULTS: Carriage of the -106 T allele was significantly associated with diabetic nephropathy in three of the four study groups. The Mantel-Haenszel combined odds ratio was 2.22 (95% CI 1.69, 2.94), P = 1.05 x 10(-8). We found no evidence for association of the microsatellite marker with nephropathy, despite moderate levels of disequilibrium between the two markers. Meta-analysis of published data yielded no evidence for association of the microsatellite marker with diabetic nephropathy in Type 2 diabetes, but varying degrees of association with diabetic nephropathy in Type 1 diabetes. CONCLUSIONS: Meta-analyses provide more convincing evidence of a role for the ALR2-106 marker than for the microsatellite marker in diabetic nephropathy (DN). More studies are now required to confirm these results and to establish whether the ALR2-106 polymorphism has a functional role in DN.     

Two promoter polymorphisms regulating interleukin-6 gene expression are associated with circulating levels of C-reactive protein and markers of bone resorption in postmenopausal women

IL-6 is a pleiotropic cytokine that plays a critical role in bone resorption. We describe two allelic variants in the IL-6 promoter, -572 and -174 G-->C, that alone and in combination influence IL-6 activity in vitro and in vivo. The association of IL-6 -572 genotypes and -572/-174 G-->C haplotypes with serum C-reactive protein (CRP), serum and urinary C-terminal cross-linking of type I collagen (a marker of bone resorption), and osteocalcin (a marker of bone formation) was investigated in a cohort of healthy postmenopausal women (n = 495; mean age +/- SD, 72 +/- 5.7 yr). Among IL-6 -572 genotypes, CRP was 37% higher (P = 0.02) and urinary C-terminal cross-linking of type I collagen was 20% higher (P = 0.01) in the presence of the C allele, whereas serum osteocalcin was not different. IL-6 -572/-174 haplotypes (G/C, G/G, and C/G) were significantly associated with all biochemical markers, and additive effects of the two polymorphic loci were found. Thus, there was a significant increase in the level of CRP (up to +79%; P = 0.007) and bone resorption markers (up to +32%; P = 0.017) with a decreasing number (from four to one) of IL-6 protective alleles -572G and -174C. In addition, there was a trend for lower age-adjusted bone mineral density at the lumbar spine in subjects with less IL-6 protective alleles (up to -9.6%; P = 0.037; P = 0.08 after further adjustment for weight). In conclusion, we describe two functional polymorphisms in the IL-6 gene regulatory region associated with IL-6 activity in postmenopausal women, both systemically (CRP) and locally in bone. As such, IL-6 polymorphisms are able to influence the risk of osteoporosis as well as other chronic disorders involving IL-6 activity.     

IL-6, IL-10 and IL-17 Gene Polymorphisms in Iranian Women with Recurrent Miscarriage

Background: Pro-inflammatory and anti-inflammatory cytokines and polymorphisms of their genes have been described to be involved in the pathogenesis of recurrent miscarriage (RM). Objective: To investigate the association between RM and five polymorphisms of cytokine genes, interleukin 10 (IL-10), (-592 A/C, -819 C/T, -1082 A/G), IL-6 (-174 C/G) and IL-17 (-197 G/A) in Iranian women. Method: Polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) was performed to determine the frequencies of the IL-6, IL-10 and IL-17 gene polymorphisms in 85 women with RM compared with 104 healthy controls. Results: The frequencies of IL- 10 promoter gene polymorphisms (-592 A/C and -819 C/T) were significantly higher in RM women than those in controls (p=0.003). However, no statistically significant differences were observed in the frequencies of IL-6 (-174 C/G), IL-10 (-1082 A/G) and IL-17 (-197 G/A) polymorphisms between RM women and controls. Conclusion: These results suggest that IL-10 gene polymorphism screening might have some relevance in patients with RM, a suggestion which requires further studies.     

中国人醛糖还原酶基因5'端(AC)n多态性与2型糖尿病肾病相关性的meta分析

目的 对中国人醛糖还原酶基因5'端(AC)n多态性与2型糖尿病合并糖尿病肾病相关性的研究进行meta分析.方法 通过文献检索收集2007年4月以前发表的中国人醛糖还原酶基因5'端(AC)n多态性与2型糖尿病合并糖尿病肾病相关性的病例-对照研究,剔除不符合要求的文献,以漏斗图检验入选文献的发表偏倚,并根据各入选文献的同质性检验结果进行数据合并,计算总OR值,meta分析采用Review Manager 4.2版统计软件.结果 共8篇文献符合条件纳入研究,入选文献无明显发表偏倚,各文献同质性检验显示有关Z-2(χ2=18.20,P=0.01)、Z+2(χ2=35.30,P<0.01)等位基因分布情况的文献间均存在显著异质性.Z～2等位基因增加2型糖尿病肾病的易感性(OR=1.72,95%CI 1.25-2.36,P<0.01),Z+6等位基因对2型糖尿病患者肾脏具有保护作用(OR=0.66,95%17/0.45-0.98,P=0.04),Z+2等位基因对糖尿病肾病的易感性无影响(OR=0.73,95%CI 0.47-1.12,P=0.15).结论 醛糖还原酶基因5'端(AC)n多态性与中国人2型糖尿病合并糖尿病肾病易感性相关,Z-2等位基因可能是2型糖尿病患者糖尿病肾病的易感基因,Z+6等位基因可能对2型糖尿病患者肾脏具有保护作用.