Polymorphisms in the Angiotensin Converting Enzyme Gene and Growth in the First Year of Life

Abnormal patterns of fetal and infant growth have been associated with an increased risk of cardiovascular disease in adulthood. Catch‐up growth during the first year of life has been associated with a higher prevalence of type 2 diabetes mellitus, whereas a lack of catch‐up growth tracks with a risk of hypertension. The role of genetic factors influencing both growth and blood pressure have not been explored. We genotyped cord blood samples from 530 singleton, Caucasian, uncomplicated pregnancies, drawn from a larger cohort of 1650 pregnancies, and related polymorphism in the angiotensin converting enzyme (ACE) gene (alleles insertion (I) or deletion (D)) with measures of size at birth and at age of 1 year. ACE genotype did not significantly influence size at birth, although there was a greater proportion of individuals with the D/D genotype born with a birth weight less than the 10^th centile (P = 0.004). The ACE I/I genotype was significantly associated with higher weight (p = 0.001), body mass index (p = 0.001) and mid arm circumference (p = 0.001) at 1 year of age compared to the ACE D/D and I/D genotypes. Individuals with the I/I genotype displayed catch‐up (gain from birth size of ≥0.6 Standard Deviation Score) in weight (p = 0.04), body mass index (p = 0.03) and mid arm circumference (p = 0.03) compared to the D/D group, the majority of which showed no change or catch‐down. The I/D genotype was distributed equally across the catch up/catch down/no change categories. The effect was more marked in males, but ACE genotype and sex of the infant contributed independently to mid arm circumference measurements and there was no interaction between the two. There was no effect of maternal or paternal ACE genotype on birth size. In a multiple linear regression model ACE genotype, socioeconomic status and sex of the infant explained 10.9% of the variance in body mass index SDS at 1 year of age. We conclude that the ACE I/I genotype is associated with a higher weight and body mass index SDS at 1 year of age, along with catch‐up in terms of these measures from birth to 1 year. The D/D genotype is associated with a greater proportion of babies, born at term, that at small for gestational age. These results suggest that due consideration should be given to the underlying genotype of an individual when evaluating the association of early human growth with the development of risk factors for cardiovascular disease. The observation of independent effects of genotype, sex of the individual and socioeconomic status on postnatal growth suggests the need to develop methodologies for the integration of genetic and environmental factors in causality modelling.     

Association between the angiotensin I-converting enzyme gene insertion/deletion polymorphism and endurance running speed in Japanese runners

We investigated the association between the angiotensin I-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism and endurance running performance in Japanese elite runners, including several Olympic athletes. The frequency of the I/I genotype was not significantly higher and the frequency of the D/D genotype was not significantly lower in elite runners compared with non-athletes. However, the frequency of the I/D genotype tended to be lower in elite runners than in non-athletes. The best performance was significantly higher for runners with the D/D genotype than for those with the I/I genotype, and the average running speed was significantly higher for those with the combined D/D + I/D genotypes than for those with the I/I genotype. There were no I/I genotypes among the five fastest marathon runners. These results suggest that the D allele of the ACE gene I/D polymorphism is associated with a high level of human endurance.     

Relation between angiotensin-converting enzyme II genotype and atrial fibrillation in Japanese patients with hypertrophic cardiomyopathy

Atrial fibrillation (AF) occurs in about 20% of patients with hypertrophic cardiomyopathy (HCM). HCM patients with AF have an increased risk for clinical decline and thromboembolism. In addition, AF is known to be associated with the atrial renin-angiotensin system (RAS). However, the relation between AF and the RAS in HCM has not been investigated. We genotyped the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in 138 HCM patients (26 with AF, 112 with sinus rhythm). Distribution of the ACE genotypes (DD, ID, and II) among the total HCM patients was 15%, 46%, and 38%. AF was documented in 3 patients with the DD genotype, 7 with the ID genotype, and 16 with the II genotype (P < 0.03 vs. sinus rhythm group). The odds of AF were 3.2-fold greater in patients with the II genotype than in those with the other genotypes (P = 0.009, 95% confidence interval = 1.3–7.8). Kaplan-Meier curves examining the time to the first documented AF event showed a significant difference between genotypes during the follow-up period (mean 116 months, P < 0.05). These findings suggest that the II genotype of the ACE gene is a significant risk factor for AF in patients with HCM. Received: December 10, 2001 / Accepted: January 25, 2002     

血管紧张素转换酶基因型与重庆地区人群原发性高血压药物治疗的关系

目的 探讨重庆地区人群血管紧张素转换酶基因（ＡＣＥ）插入／缺失（Ｉ／Ｄ）多态性与原发性高血压及药物治疗的关系。方法 用多聚酶链反应直接扩增ＡＣＥ基因第１６内含子,对１１４名正常人和７５例原发性高血压患者进行了分析,同时对４９例原发性高血压患者用血管紧张素转换酶抑制剂（ＡＣＥＩ,依拉普利）和钙通道阻滞剂（ＣＣＢ,菲洛地平）进行自身交叉治疗,并比较降压效果。结果 原发性高血压患者ＡＣＥ基因的ＤＤ型频率     

Insertion/deletion polymorphism in the angiotensin-converting enzyme gene associated with macroangiopathy and blood pressure in patients with non-insulin-dependent diabetes mellitus

In the search for new risk factors for diabetic macroangiopathy the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene was studied in 237 consecutive patients (125 men and 112 women) with non-insulin-dependent diabetes. The female population showed an excess of ischemic electro-cardiographic changes or definite myocardial infarctions in the patients homozygous for the deletion [D/D; odds ratio (OR) 2.8; 95% confidence interval (CI) 1.4–5.3] and in the insertion/deletion heterozygotes (I/D; OR 1.8; CI 1.1–3.1) compared with the patients homozygous for the insertion (I/I). In the total series coronary heart disease, cerebrovascular disease, and claudication were more often observed in the patients with I/D (OR 1.5; CI 1.0–2.2) or the D/D genotype patients (OR 1.7; CI 1.1–2.6) than in those with the genotype I/I. The systolic blood pressure was lower in patients with genotype I/I (138±19 mmHg) than in those with the genotype I/D (149±22 mmHg) or D/D (150±21 mmHg; P<0.02). The prevalence of hypertension and the median urinary albumin excretion rate also tended to be lowest in the I/I genotype patients. Multiple logistic analysis revealed that in women the angiotensin-converting enzyme D/D genotype is independently associated with coronary heart disease. Our findings suggest that variation at the angiotensin-converting enzyme gene locus is one of the factors involved in the predisposition of diabetic patients to the development of arterial disease and hypertension.Abbreviations ACE Angiotensin-converting enzyme - CHD Coronary heart disease - NIDDM Non-insulin-dependent diabetes mellitus     

Polymorphism of genes of the renin-angiotensin system ACE, ATIR, and AT2R in patients with pulmonary tuberculosis

The investigation was aimed at testing the hypothesis on the possible role of some genes of the renin-angiotensin system in the formation of innate immunity to tuberculosis. It is known that insertion-deletion (I/D) polymorphism of the gene encoding the angiotensin-converting enzyme (ACE) influences the concentration of angiotensin II in the human organism and, indirectly, many stages of metabolism. On one hand, homozygotes of deletion in the ACE gene (DD genotype) are characterized with obesity, arterial hypertension, hypocholesterolemia, and some other pathological conditions. On the other hand, it was demonstrated that hypercholesterolemia is common pathology for patients with pulmonary tuberculosis (C. Perez-Guzman et al., 2005). The investigation of insertion-deletion polymorphism of the ACE gene (genotypes DD, ID and II), single nucleotide polymorphism at position 1166 of the AT1R gene (1166 A/C), and analogous transversion at position 3123 of the AT2R gene (3123 A/C) was carried out. A group of 200 patients with tuberculosis 202 patients with essential hypertension and 208 healthy individuals were analyzed. A group of patients with essential hypertension was used as a contrast sample. According to hypothesis, a statistically significant excess number was found of carriers of genotype DD (ACE) in patients with hypertension as compared to the group of patients with tuberculosis (χ² = 9.64; ρ = 0.0019; OR = 2.0; CI 1.2, 3.3). The tendency toward an increase in the amount of DD genotypes was observed in comparisons of patients with tuberculosis and healthy patients with hypertension, although these differences did not reach significant values in the given study. A comparison of genotypes and allelotypes in group of patients with tuberculosis and both control groups (healthy and patients with hypertension) was performed. A significant difference was observed in the group of male patients with tuberculosis, though not female, when comparing with control groups. It had been demonstrated that the most important contribution is made by the ACE and AT2R genes. Genotype ID + 3123C (genes ACE and AT2R) was found significantly more often in male patients with tuberculosis than in the control group of healthy individuals (χ² = 9.70; ρ = 0.002; OR = 2.3; CI 1.2s-4.3). The obtained results were discussed.     

新疆哈萨克族隔离群血管紧张素转换酶基因I/D多态性与高血压病的关系

目的 探讨哈萨克族人群血管紧张素转换酶(angiotensin converting enzyme,ACE)基因第16内含子中的插入／缺失(insertion／deletion，I／D)多态性是否为高血压病(essential hypertension，EH)的遗传易患因素。方法 应用聚合酶链反应检测了新疆巴里坤县201例哈萨克族高血压病患者和151名正常人的ACE基因16内含子I／D多态性。结果 哈萨克族正常人群及高血压患者的ACE基因I／D多态性DD、ID、Ⅱ基因型频率分布分别为0．17、0．43、0．40和0．18、0．52、0．30，D和I等位基因分布频率分别为0．39和0．61和0．44、0．56，符合Hardy-Weinberg平衡。群体相关分析结果表明，ACE基因的D及I等位基因分布在高血压病组及正常血压组的差异无显著性(x^2＝1．98，P＝0.16)；基因型频率之间差异也无显著性(x^2＝4．0，P＝0．14)。结论 ACE基因16内含子I／D多态性可能与新疆巴里坤哈萨克族高血压病无关。     

ACE (I/D) polymorphism and response to treatment in coronary artery disease: a comprehensive database and meta-analysis involving study quality evaluation

Background  

The role of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in modifying the response to treatment modalities in coronary artery disease is controversial.     

The ACE I allele is associated with increased risk for ruptured intracranial aneurysms

Genetic and environmental factors play roles in the aetiology of ruptured intracranial aneurysms. Hypertension has been reported as a risk factor for intracranial aneurysm haemorrhage. We have tested if genotypes at the angiotensin converting enzyme (ACE) gene locus are associated with ruptured intracranial aneurysms. The insertion/deletion polymorphism in the ACE gene was genotyped in 258 subjects presenting in East Anglia with ruptured intracranial aneurysms (confirmed at surgery or angiographically) and 299 controls from the same region. ACE allele frequencies were significantly different in the cases and the controls (alleles χ²₁=4.67, p=0.03). The I allele was associated with aneurysm risk (odds ratio for I allele v D allele = 1.3 (95% CI=1.02-1-65); odds ratio for II v DD genotype = 1.67 (95% CI=1.04-2.66)). The I allele at the ACE locus is over-represented in subjects with ruptured intracranial aneurysms. These data are supported by non-significant trends in the same direction in two previous smaller studies. Thus, this allele may be associated with risk for ruptured intracranial aneurysms.


Keywords: ACE I allele; ruptured intracranial aneurysms     

Does the ACE I/D polymorphism, alone or in combination with the ACTN3 R577X polymorphism, influence muscle power phenotypes in young, non-athletic adults?

We investigated the association of the angiotensin converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism, alone or in combination with the α-actinin-3 gene (ACTN3) R577X polymorphism, with jumping (vertical squat and counter-movement jump tests) and sprint ability (30 m dash) in non-athletic, healthy young adults [N = 281 (214 male), mean (SD) age 21 (2) years]. We did not observe any effect of the ACE I/D polymorphism on study phenotypes. We repeated the analyses separately in men and women and the results did not materially change. Likewise, the mean estimates of the study phenotypes were similar in subjects with the genotype combinations ACE II + ID and ACTN3 XX or ACE DD and ACTN3 RR + RX. We found no association between the ACE DD and ACTN3 RR + RX genotype combination and performance (≥90th of the sex-specific percentile). In summary, though the ACE I/D polymorphism is a strong candidate to modulate some exercise-related phenotypes or athletic performance status, this polymorphism, alone or in combination with the ACTN3 R577X polymorphism, does not seem to exert a major influence in the muscle ‘explosive’ power of young healthy adults, as assessed during multi-joint exercise tests.     

Polymorphism of the angiotensin-converting enzyme gene and cardiovascular disease

The angiotensin-converting enzyme (ACE) is an integral part of two enzymatic cascades, one leading to the generation of angiotensin II and the other to the degradation of bradykinin. The great variety of cardiovascular effects mediated by these vasoactive peptides and the efficacy of ACE inhibitors in the treatment of hypertension and heart failure emphasize the prominent role of ACE in the cardiovascular system. Early in this decade convincing experimental evidence demonstrated the induction of this enzyme in several pathophysiological conditions, including myocardial infarction and left ventricular hypertrophy. In parallel, a deletion/insertion (D/I) polymorphism of the human ACE gene was characterized that is related to 14–50% of the interindividual variance in serum ACE activity. More recently this polymorphism has been implicated in the pathogenesis of a variety of cardiovascular disorders, including myocardial infarction, left ventricular hypertrophy, hypertension, diabetic and IgA nephropathy, carotid artery thickening, and lacunar cerebral stroke. However, the associations between the ACE D/I polymorphism and most of these conditions were found to be inconsistent when additional populations were investigated. This contribution reviews the current evidence on the relationship between the ACE D/I polymorphism and cardiovascular disease.     

Combinational effect of genes for the renin–angiotensin system in conferring susceptibility to diabetic nephropathy

To elucidate the role of the renin–angiotensin system (RAS) in diabetic nephropathy, we examined the association between diabetic nephropathy in a large cohort of Japanese type 2 diabetic patients and polymorphisms within the genes that encode angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II receptor type 1 (AGTR1). Single nucleotide polymorphisms (SNPs) within these genes were genotyped using invader assay in 747 nephropathy cases and 557 control subjects. Eight SNPs within the ACE gene were significantly associated with diabetic nephropathy (P<0.05), including five SNPs in almost complete linkage disequilibrium to the insertion/deletion polymorphism in the 16th intron (P=0.01, odds ratio =1.34, 95% CI 1.07–1.69). Three SNPs within the AGT, including M235T and one SNP in the AGTR1, were also significantly associated with nephropathy (M235T P=0.01, odds ratio =0.74, 95% CI 0.59–0.94). In addition, we found that the allelic mRNA expression corresponding to the 235M allele was significantly higher than that for the 235T allele in normal kidney tissues. Furthermore, we found a significant additional effect of these three genes by a step-wise logistic regression analysis (final empirical P value =0.00005). We concluded that RAS gene polymorphisms may contribute to the susceptibility to diabetic nephropathy in type 2 diabetes. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Comparative analysis of associations between polymorphic variants of the F2, F5, GP1BA, and ACE genes and the risk of developing stroke in Russian and Ukrainian populations

We performed comparative analysis of associations between the F2 gene G20210A polymorphism, the F5 gene G1691A polymorphism, the GP1BA gene -5T/C polymorphism, the ACE gene insertion/deletion (I/D) polymorphism and the risk of developing stroke in two samples drawn from ethnic Russian and ethnic Ukrainian populations. It has been shown, that among the Russian population, the risk of developing ischemic stroke is increased in DD genotype individuals (odds ratio (OR) = 1.4, 95% confidence interval (CI) [1.05; 1.78], p = 0.02), whereas the I/I and I/D genotypes are associated with a decreased risk of developing stroke (OR = 0.7, 95% CI [0.56; 0.95], p = 0.02). In the ethnic Ukrainian sample, differences in the distribution of genotypes and allele frequencies between stroke patients and the control group of subjects with regard to this polymorphic locus are statistically unreliable and the ACE gene I/D polymorphism is unassociated with the risk of developing stroke in the Ukrainian population (OR = 0.8, 95% DI[0.48; 1.32], p = 0.45). The F2 gene G20210A polymorphism, the F5 gene G1691A polymorphism, and the GP1BA gene -5T/C polymorphism are unassociated with stroke risk factor across both ethnic samples.     

Effect of angiotensin converting enzyme gene I/D polymorphism in South Indian children with nephrotic syndrome

Nephrotic syndrome is one of the most common childhood kidney diseases. It is mostly found in the age group of 2 to 8 years. Around 10%–15% of nephrotic syndrome cases are non-responders of steroid treatment (SRNS). Angiotensin converting enzyme (ACE) (I/D) gene association studies are important for detecting kidney disease and herein we assessed the association of ACE (I/D) polymorphism with nephrotic syndrome in South Indian children. We recruited 260 nephrotic syndrome (162 boys and 98 girls) and 218 (140 boys and 78 girls) control subjects. ACE I/D polymorphism was analyzed by PCR using genotype allele specific primers. In ACE (I/D), we did not find significant association for the ungrouped data of nephrotic syndrome children and the control subjects. Kidney biopsies were done in 86 nephrotic syndrome cases (minimal change disease, n = 51; focal segmental glomerulosclerosis, n = 27; diffuse mesangial proliferation, n = 8). We segregated them into the minimal change disease / focal segmental glomerulosclerosis groups and observed that the ACE 'D' allele was identified with borderline significance in cases of focal segmental glomerulosclerosis and the 'Ⅰ' allele was assessed as having very weak association in cases of minimal change disease. 'Ⅱ' genotype was weakly associated with minimal change disease. Gender specific analysis revealed weak association of 'ID' genotype with female nephrotic syndrome in females. Dominant expression of DD genotype was observed in males with nephrotic syndrome. Our finding indicated that ACE (I/D) has moderate association with focal segmental glomerulosclerosis. However, due to the limited number of biopsy proven focal segmental glomerulosclerosis subjects enrolled, further studies are required to confirm these results.     

血管紧张素转换酶基因I-D多态性与湘西侗族人群高血压病的关系

目的 探讨血管紧张素转换酶(angiotensin converting enzyme,ACE)基因第16内含子中的插入/缺失(insertion/deletion,I-D)多态性与湘西通道侗族人群高血压病(essential hypertension,EH)之间的关系.方法 应用聚合酶链反应检测了湘西通道县93例侗族高血压病患者和99名正常对照的ACE基因16内含子I-D多态性.结果 湘西通道侗族正常对照和高血压病组ACE基因I-D多态位点Ⅱ、ID、DD基因型频率分别为47.5%、42.4%、10.1%和40.9%、41.9%、17.2%,两组I-D等位基因频率分别为68.7%/31.3%和61.8%/38.2%.两组基因型频率和等位基因频率分别经χ2检验,等位基因频率分布无统计学差异(χ2=1.04,P=0.31),基因型频率差异亦无统计学意义(χ2=2.26,P=0.32).结论 ACE基因16内含子I-D多态性可能与湘西通道侗族人群高血压病之间没有关联.     

The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia

Preeclampsia is associated with thrombosis of the intervillous or spiral artery. A deletion/insertion polymorphism (4G or 5G) in the promoter of the plasminogen activator inhibitor type 1 (PAI-1) gene is suggested to be involved in regulating the synthesis of the inhibitor, 4G allele, being associated with the enhanced gene expression and plasma PAI-1 levels. We assessed the association between preeclampsia and the 4G/5G polymorphism of the PAI-1 gene in 115 preeclamptic patients, 210 pregnant controls, and 298 healthy volunteer controls. The frequency of the homozygotes for the 4G allele was significantly higher in the patients than in the control pregnant women (P = 0.04) or in the healthy volunteers (P = 0.02). The 4G allele frequency was also significantly higher in the patients than in the control group of pregnant women (P = 0.03) and in the healthy volunteers (P = 0.02). These results suggest that the presence of the 4G/4G genotype of the PAI-1 gene is one of the risk factors for preeclampsia. Received: October 14, 1999 / Accepted: January 4, 2000     

血管紧张素转换酶基因插入/缺失多态性在人群中的分布及其与原发性高血压的关系

目的　研究血管紧张素转换酶 (angiotensin converting enzyme,ACE)基因 I/ D多态性在人群中的分布特征及其与原发性高血压的关系。方法　应用 PCR方法对 2 966名开滦矿务局职工进行 ACEI/ D基因型检测 ,并分析比较。结果　研究人群中 II、ID、DD基因型分布频率分别为 41.5%、3 8.4%、2 0 .1% ,I、D等位基因分布频率分别为 60 .7%和 3 9.3 %。ACE DD基因型在高血压组 (13 0 8例 )和对照组(1658名 )的频率分别为 18.9%和 2 1.0 % ,差异无显著性 (P>0 .0 5) ,按年龄及性别分层后差异也无显著性(P>0 .0 5)。DD基因型及 D等位基因分布频率有随年龄的增长而下降的趋势 (P<0 .0 0 1)。结论　 ACE I/D多态性与原发性高血压无关 ,基因型及等位基因的分布因年龄不同而不同 ,并提示具有 DD基因型特征的人群早期死亡危险的增加     

The ACE gene and Alzheimer's disease susceptibility

A recent study suggested that the insertion (I) allele in intron 16 of the angiotensin converting enzyme gene (ACE) is associated with Alzheimer's disease (AD) risk. In our series of 239 necropsy confirmed late onset AD cases and 342 elderly non-demented controls aged >73 years, we found significantly different ACE genotype distributions in the case and control groups (p=0.007). Homozygotes for both the I and D alleles were associated with a higher risk compared to DI heterozygotes. While the APOE ε4 allele was strongly associated with AD risk in our series, we found no evidence for an interaction between the APOE and ACE loci. In addition, no interactions were observed between ACE and gender or age at death of the AD cases. A meta-analysis of all published reports (12 case-control series in total) suggested that both the II and ID ACE genotypes are associated with increased AD risk (odds ratio (OR) for II v DD 1.36, 95% confidence interval (CI)=1.13-1.63, OR for DI v DD 1.33, 95% CI=1.14-1.53, p=0.0002).


Keywords: Alzheimer's disease; ACE gene; I allele     

HLA‐G 14‐bp polymorphism affects the age of onset in Type I Diabetes Mellitus

Type I diabetes mellitus (T1DM) is an organ‐specific autoimmune disorder affecting the insulin‐producing pancreatic cells. T1DM genetic association studies have so far revealed the involvement of more than 40 loci, with particularly strong associations for the human leucocyte antigens (HLA). Further to the well‐established HLA class II associations, the immunomodulatory elements in the telomeric major histocompatibility complex locus, specifically nonclassical HLA class I, were also associated with T1DM, either in conferring susceptibility or by contributing to the overall pathogenesis. This study investigates the involvement of a 14‐bp deletion polymorphism (rs371194629) at the 3′ untranslated region of HLA‐G in the context of T1DM and age of onset. The frequency of the polymorphism was determined in unrelated T1DM Cypriot patients and findings that emerge from this study show a strong association between the HLA‐G 14‐bp polymorphism and T1DM with respect to the age of onset. Specifically, the deletion/deletion (DEL/DEL) genotype was found to be associated with an early age of onset (P = 0.001), while the presence of the insertion allele (INS) was associated to a later age of onset (P = 0.0001), portraying a possible dominant effect over the deletion allele, a role in delaying disease onset and an overall involvement of HLA‐G in the pathogenesis of type I diabetes mellitus.     

Association between ACE polymorphisms and osteoarthritis susceptibility

Objective: The present study was designed to investigate the association of angiotensin-converting enzyme (ACE) rs4343 and rs4362 polymorphisms with the susceptibility to osteoarthritis (OA). Methods: 109 knee OA patients and 114 healthy people were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to perform the genotyping for two groups and the linkage disequilibrium and haplotype were analyzed using Haploview software. The differences of genotype and allele frequencies were analyzed by χ² test and Fisher’s exact test. The relationship between ACE polymorphisms and OA susceptibility was represented by odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: The genotypes distributions of ACE rs4343 and rs4362 polymorphisms in control groups were accordance with HWE. ACE rs4343 polymorphism was associated with the significantly increased risk of OA (AG vs. AA: OR=2.41, P=0.003; GG vs. AA: OR=5.35, P=0.015; G vs. A: OR=2.27, P<0.001). Similarly, rs4362 polymorphisms was also a risk factor for OA (CT vs. CC: OR=2.60, P=0.005; TT vs. CC: OR=3.15, P=0.003; T vs. C: OR=1.88, P=0.001). The result of haplotype analysis showed complete linkage disequilibrium in rs 4343 and rs 4362 polymorphisms. The G-T haplotype significantly increased OA susceptibility, but A-C is a protective factor for the occurrence of OA. Conclusion: Significant correlation exists between ACE rs4343 and rs4362 polymorphisms and OA. In haplotype analysis, A-C haplotype may provide protection against OA, and G-T haplotype may be a risk factor for the development of OA.