Novel 8-wire basket catheter is useful for endoscopic removal of common bile duct stones up to 10 mm: A multicenter prospective study.

BACKGROUND/PURPOSE: Endoscopic treatment of common bile duct (CBD) stones involves the use of basket or balloon catheters; however, what is the appropriate device remains controversial. In this study we aimed to prospectively evaluate the usefulness of a novel 8-wire helical basket (8WB) catheter made of Nitinol for the removal of CBD stones ≤10 mm. METHODS: We conducted a multicenter prospective trial. Patients with CBD stones ≤10 mm were enrolled. The primary endpoint was the rate of complete stone removal within 10 min using the 8WB. The number of cases was determined using a previous study of stone removal by a conventional basket catheter as a historical control. RESULTS: A total of 155 patients were enrolled and 139 were ultimately included in the analysis. Patients with a single stone were the most common (84 cases, 60.4%), with a median maximum stone diameter of 5 mm. The median stone removal time using the 8WB was 6 min. The complete stone removal rate was 95.0% (132/139). Adverse events were observed in 14 patients (10.1%). CONCLUSIONS: The novel 8WB catheter is useful in the treatment of CBD stones ≤10 mm, presenting a high complete stone removal rate in this study. TRIAL REGISTRATION NUMBER: jRCT1032200324.

A new device for fiducial registration of image-guided navigation system for liver RFA.

PURPOSE: Radiofrequency ablation for liver tumors (liver RFA) is widely performed under ultrasound guidance. However, discriminating between the tumor and the needle is often difficult because of cavitation caused by RFA-induced coagulation. An unclear ultrasound image can lead to complications and tumor residue. Therefore, image-guided navigation systems based on fiducial registration have been developed. Fiducial points are usually set on a patient's skin. But the use of internal fiducial points can improve the accuracy of navigation. In this study, a new device is introduced to use internal fiducial points using 2D US. METHODS: 3D Slicer as the navigation software, Polaris Vicra as the position sensor, and two target tumors in a 3D abdominal phantom as puncture targets were used. Also, a new device that makes it possible to obtain tracking coordinates in the body was invented. First, two-dimensional reslice images from the CT images using 3D Slicer were built. A virtual needle was displayed on the two-dimensional reslice image, reflecting the movement of the actual needle after fiducial registration. A phantom experiment using three sets of fiducial point configurations: one conventional case using only surface points, and two cases in which the center of the target tumor was selected as a fiducial point was performed. For each configuration, one surgeon punctured each target tumor ten times under guidance from the 3D Slicer display. Finally, a statistical analysis examining the puncture error was performed. RESULTS: The puncture error for each target tumor decreased significantly when the center of the target tumor was included as one of the fiducial points, compared with when only surface points were used. CONCLUSION: This study introduces a new device to use internal fiducial points and suggests that the accuracy of image-guided navigation systems for liver RFA can be improved by using the new device.

Evaluation of hepatocellular carcinoma tumor vascularity using contrast-enhanced ultrasonography as a predictor for local recurrence following radiofrequency ablation.

PURPOSE: The purpose of this study was to evaluate whether the hypervascularity of hepatocellular carcinomas (HCCs) on contrast-enhanced ultrasonography (CEUS) prior to radiofrequency ablation (RFA) is a significant risk factor for local recurrence after RFA. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Overall, 208 patients (mean age, 71.7 years; range, 50-87 years; 137 men, 71 women) with 282 HCCs treated with RFA were analyzed retrospectively. The mean maximum tumor diameter was 15.7mm. We compared the abilities of CEUS and contrast-enhanced computed tomography (CECT) to detect hypervascularity in HCCs. We then classified the HCCs into two groups according to the arterial-phase CEUS findings: a "hypervascular group" with whole or partial hypervascular areas within the lesions compared with the surrounding liver parenchyma, and a "non-hypervascular group" with isovascular or hypovascular areas within the lesions. We assessed the cumulative rate of local recurrence after RFA, and we also evaluated the risk factors for local recurrence using a univariate analysis. RESULTS: The detection rate for hypervascular HCCs was significantly higher using CEUS (78%, 221/282) than that using CECT (66%, 186/282) (P<0.001). Using the CEUS findings, the cumulative rate of local recurrence was significantly higher in the hypervascular group (41.2%, 56/221) than in the non-hypervascular group (18.4%, 6/61) (P=0.007). A univariate analysis revealed that hypervascularity on CEUS was an independent risk factor for local recurrence (P=0.010). CONCLUSION: Hypervascularity in HCCs as observed using CEUS is a significant risk factor for local recurrence after RFA.

Assessment of Self-Efficacy and its Relationship with Frailty in the Elderly.

Objective It has been increasingly recognized in various clinical areas that self-efficacy promotes the level of competence in patients. The validity, applicability and potential usefulness of a new, simple model for assessing self-efficacy in the elderly with special reference to frailty were investigated for improving elderly patients' accomplishments. Methods The subjects of the present study comprised 257 elderly people who were members of the New Elder Citizen Movement in Japan and their mean age was 82.3±3.8 years. Interview materials including self-efficacy questionnaires were sent to all participants in advance and all other physical examinations were performed at the Life Planning Center Clinic. Results The internal consistency and close relation among a set of items used as a measure of self-efficacy were evaluated by Cronbach's alpha index, which was 0.79. Although no age-dependent difference was identified in either sex, gender-related differences in some factors were noted. Regarding several parametric parameters, Beck's inventory alone revealed a significant relationship to self-efficacy in both sexes. Additionally, non-parametric items such as stamina, power and memory were strongly correlated with self-efficacy in both sexes. Frailty showed a significant independent relationship with self-efficacy in a multiple linear regression model analysis and using Beck's inventory, stamina, power and memory were identified to be independent factors for self-efficacy. Conclusion The simple assessment of self-efficacy described in this study may be a useful tool for successful aging of elderly people.

A case of multiple hepatic lesions associated with methotrexate-associated lymphoproliferative disorder.

Patients receiving methotrexate (MTX) for the treatment of autoimmune disease are at a high risk of developing lymphoproliferative disorders (LPD), the so-called methotrexate-associated lymphoproliferative disorders (MTX-LPD). We recently performed abdominal ultrasonography (US) in a patient with rheumatoid arthritis (RA) who had developed hepatic dysfunction during the course of MTX therapy; the examination revealed multiple well-demarcated hepatic tumors with slightly irregular borders, the largest one measuring 9 cm in diameter. In view of the finding of portal and hepatic veins perforating the tumor, we suspected a diagnosis of malignant lymphoma and performed a hepatic tumor biopsy. Histopathological examination of the biopsy specimens revealed a diagnosis of diffuse large B-cell lymphoma, and we made a final diagnosis of MTX-LPD. MTX treatment was discontinued, which resulted in rapid resolution of the lesions. Resolution of MTX-LPD can be obtained just by discontinuation of MTX treatment. In patients receiving MTX therapy who are found to have hepatic tumors perforated by the portal vein and/or hepatic vein on abdominal US, it is advisable to perform hepatic tumor biopsy to facilitate differential diagnosis of MTX-LPD and enable a definite diagnosis.

A haplotype of the GOSR2 gene is associated with myocardial infarction in Japanese men.

AIMS: The Golgi SNAP Receptor Complex Member 2 (GOSR2) gene is a Golgi-associated soluble factor attachment receptor (SNARE) protein. Some single-nucleotide polymorphisms (SNPs) in the GOSR2 gene have been found to be associated with myocardial infarction (MI). The aim of the present study was to assess the association between the human GOSR2 gene and MI using a haplotype-based case-control study. METHODS: A total of 238 MI patients and 284 controls were genotyped for the five SNPs used as genetic markers for the human GOSR2 gene (rs197932, rs3785889, rs197922, rs17608766, and rs16941382). Data were analyzed for three separate groups: the total subjects, men, and women. RESULTS: The overall distribution of the haplotypes in the total subjects and the men was significantly different between the MI patients and the control subjects (p=0.001, p=0.005, respectively). Additionally, the frequency of the T-G-G haplotype (rs197932-rs3785889-rs197922) for men was significantly lower in the MI patients than in the control subjects (p=0.040). Multiple logistic regression analysis also revealed that the frequency of the subjects with the T-G-G haplotype (homozygous and heterozygous diplotypes) was significantly lower compared with subjects without this haplotype in men after adjustment for the major confounding factors (odds ratio=0.455, p=0.041). CONCLUSIONS: The results of this study indicate that the T-G-G haplotype may be a protective genetic marker for MI in Japanese men.

Changes in ankle brachial pulse wave velocity during a five-year follow-up period in older Japanese adults: sub-analysis results of the health research volunteer study in Japan.

OBJECTIVE: Brachial-ankle pulse wave velocity (baPWV) is a measure of arterial stiffness. However, precisely how aging, hypertension and other factors influence this in progressively stiffening large arteries, especially in older adults, remains uncertain. We examined changes in arterial stiffness in a population of active older Japanese adults using a five-year follow-up cohort study. METHODS: Comprehensive geriatric assessments were performed in socially active adults over the age of 70 years at The Life Planning Center Clinic in Tokyo. Clinically acceptable baPWV measurements at baseline and at the end of the study were obtained in 257 individuals (115 men, baseline mean age of 78±4 years; 142 women, baseline mean age of 77±4 years) classified into four groups based on the use of antihypertensive interventions at the end of the study: Group 1 (112 normotensives), Group 2 (49 hypertensives without medication use), Group 3 (39 hypertensives with medication use initiated during the follow-up period) and Group 4 (57 hypertensives receiving medications throughout the follow-up period). RESULTS: During the follow-up period, Group 1 exhibited no changes in blood pressure with increases in baPWV. Group 2 exhibited increases in blood pressure and baPWV. Both Groups 3 and 4 exhibited decreases in blood pressure without any changes in baPWV. Other factors such as age, gender and the hemoglobin level could also have influenced baPWV. CONCLUSION: Arterial stiffness increases with aging; however, antihypertensive medications were found to provide protective effects against the development of arterial stiffness during a five-year follow-up period. Other factors that modify baPWV were also identified.

Association of the smoothelin (SMTN) gene with cerebral infarction in men: a haplotype-based case-control study.

Smoothelin is a specific type of cytoskeletal protein found in smooth muscle cells (SMCs). Several previous research studies have examined the relationship between smoothelin and atherosclerotic plaque. The aim of the present study was to further assess the association between the human SMTN gene and cerebral infarction (CI) using a haplotype-based case-control study. A total of 168 CI patients and 259 supercontrols were genotyped for the five single-nucleotide polymorphisms (SNPs) used as genetic markers for the human SMTN gene (rs2074738, rs5997872, rs56095120, rs9621187 and rs10304). Data were analyzed for three separate groups that included total subjects, men and women. The genotypic distribution of rs10304 for men showed a significant difference between the control and CI groups. In addition, the frequency of the C-T-T-A haplotype (established by rs5997872, rs56095120, rs9621187 and rs10304) was significantly higher in the CI versus the control group (p = 0.013), while the frequency of the C-A-T-G haplotype (established by rs5997872, rs56095120, rs9621187 and rs10304) in the CI group was significantly lower than that seen in the controls (p = 0.021). In conclusion, we confirmed that the haplotype constructed using rs5997872, rs56095120, rs9621187 and rs10304 was a useful genetic marker of CI in Japanese men.

A pilot trial to predict frailty syndrome: the Japanese Health Research Volunteer Study.

Most definitions of frailty utilize US populations in their development. The concept of frailty has not been well studied in Japan, which has the largest percentage of older patients (per capita) in the world. We created a 5-year prospective cohort study of community-dwelling older Japanese adults. Participants were not frail at baseline, based on our definition adapted from the Canadian Study for Health and Aging Clinical Frailty Scale. Participants underwent a comprehensive geriatric assessment (CGA) at baseline, and final assessments were either in person or via mailed survey. We enrolled 407 individuals (184 men, mean age 78 ± 4 years; 223 women, mean age 77 ± 4 years). Sixty-five participants met criteria for frailty by the end of the study. In univariate analyses, eighteen separate parameters were associated with frailty, some of which included: age, gender, handgrip, timed walk, systolic blood pressure, pulse pressure, cognitive status, living alone, and hearing deficits. In multivariate analyses, the following elements remained associated with frailty: timed walk, pulse pressure, cognition deficits and hearing deficits. We established cut-off points for timed walk (5m/3s) and pulse pressure (60 mmHg). We then created a simple additive score for these four factors (present = 1; absent = 0). A score of 0 had a 93% negative predictive value for frailty while a score of 4 had a 70% positive predictive value. While further study is needed, this work creates an easy-to-administer tool that may be generalizable to other populations.

Effects of aging and persistent prehypertension on arterial stiffening.

An age-related association of blood pressure in the non-hypertensive range (non-hypertensive blood pressure) to the cardiovascular mortality has been demonstrated. This prospective study was conducted to examine the effects of age, persistence of pre-hypertension (preHYP) during the study period, and the interaction between these factors on the rate of progression of arterial stiffening. Among 1563 healthy Japanese subjects without hypertension (age range: 29-95 years), the brachial-ankle pulse wave velocity (baPWV) was measured twice (i.e., at baseline and 5-6 years later). The adjusted (including for blood pressure) value of the annual rate of increase of the baPWV during the study period (delPWV) increased in a linear manner along with the age category (categorized into 29-39 years, 40-59 years, and 60 years or older for this study) and the evolutional category of non-hypertensive blood pressure during the study period (categorized into persistence of normal blood pressure, borderline evolution, and persistence of preHYP), and a significant interaction between the two in relation to the delPWV was also noted (non-standardization coefficient=5.08 [95% confidence interval=3.24-6.92], F-value=29.40, P<0.01). In conclusion, the present study suggests that persistence of preHYP is associated with accelerated structural stiffening of the large- to middle-sized arteries, and that age may exert a synergistic effect on this acceleration of arterial stiffening. Thus, persistence of preHYP also appears, like hypertension, to be associated with progressive vascular damage, and this progression may be more pronounced in middle-aged and elderly subjects.

The haplotype of the CACNA1B gene associated with cerebral infarction in a Japanese population.

Cerebral infarction (CI) is thought to be a multifactorial disease that is affected by several environmental factors and genetic variants. N-type voltage-gated calcium channels (VGCCs), which are expressed primarily in the neurons, have various roles in neuronal functions and are especially involved with neurotransmitter release at the sympathetic nerve terminals. We considered the α1B subunit of the N-type voltage-gated calcium channel (CACNA1B) to be representative of the general characteristics of this channel type. The aim of the present study was to assess the association of the human CACNA1B gene with the occurrence of CI via a haplotype-based case-control study that used single nucleotide polymorphisms (SNPs) from the Japanese population. A total of 165 CI patients and 314 controls were enrolled in the case-controlled studies that examined three SNPs of the human CACNA1B gene (rs7042521, rs11137351, rs10780199). There were significant differences between the CI and control groups for the overall distribution of the genotypes and the presence of the recessive rs10780199. Multiple logistic regression analyses revealed that even after adjusting for confounding factors (odds ratio: 1.716), the frequencies of the A/G and G/G genotypes of rs10780199 in the CI group were significantly higher than those observed in the control group (p = 0.021). Furthermore, the C-C-G and G-G-G haplotypes of rs7042521-rs11137351-rs10780199 were significantly more frequent in the CI group than in the control group (p = 0.024 and p < 0.000). In conclusion, significant differences were noted between the CI and control patients for the specific SNPs and haplotypes in the CACNA1B gene. The results indicate that these polymorphisms and haplotypes might be genetic markers for CI.

Development and validation of a 15-item Japanese Health Knowledge Test.

BACKGROUND: Health literacy affects the acquisition of health knowledge and is thus linked to health outcomes. However, few scales have been developed to assess the level of health knowledge among the general public. METHODS: The 15-item Japanese Health Knowledge Test (J-HKT) was developed by using item response theory to score an item pool. We examined the construct validity of the J-HKT in relation to health literacy items, and analyzed the sociodemographic and behavioral factors associated with poor health knowledge. RESULTS: We enrolled 1040 adult participants (mean age, 57 years; women, 52%). The 15 items that best identified people with poor health knowledge were selected. For all items on the J-HKT, the information function curves had a peak in the negative spectrum of the latent trait. As compared with participants reporting high levels of income, educational attainment, and literacy, those with low levels of income, education, and literacy had a lower total score on the J-HKT. As compared with non/light drinkers, moderate and heavy drinkers had lower total scores on the J-HKT. CONCLUSIONS: The J-HKT may prove useful in measuring health knowledge among the general public, and in identifying and characterizing those with poor health knowledge.

Association of the purinergic receptor P2Y, G-protein coupled, 2 (P2RY2) gene with myocardial infarction in Japanese men.

BACKGROUND: Atherosclerosis leads to myocardial infarction (MI) and P2RY2 plays an important role in this process. The aim of the present study was to investigate the association between human P2RY2 and MI via a haplotype-based case-control study that additionally analyzed the group by sex. METHODS AND RESULTS: The 310 MI patients and 254 controls were genotyped for 5 single-nucleotide polymorphisms (SNPs) of the human P2RY2 gene (rs4944831, rs1783596, rs4944832, rs4382936, rs10898909). Data were separately analyzed for the total, male, and female subjects. For men, the GA+AA genotype of rs10898909 was significantly higher in MI patients as compared with controls (P=0.040). Logistic regression analysis found a significant difference for the genotype (P=0.016). As compared with controls, the frequencies of the C-A and T-C-A haplotypes were significantly higher (P=0.016, and P=0.045, respectively) in men, whereas the frequencies of the C-G and T-A-A haplotypes were significantly lower (P=0.023, and P=0.025, respectively) in MI patients. CONCLUSIONS: The GA+AA genotype, as well as the C-A and T-C-A haplotypes, of human P2RY2 could be genetic markers for MI in Japanese men.

Purinergic receptor P2Y, G-protein coupled, 2 (P2RY2) gene is associated with cerebral infarction in Japanese subjects.

G-protein-coupled purinergic receptor P2Y2 (P2RY2) has an important role in the process of atherosclerosis related to cerebral infarction (CI). The aim of this study was to investigate the relationship between the P2RY2 gene and CI through a haplotype-based case-control study, including the separate analysis of two gender groups. A total of 237 CI patients and two control groups (control 1, 254; control 2, 255) were genotyped for five single nucleotide polymorphisms (SNPs) in the human P2RY2 gene (rs4944831, rs1783596, rs4944832, rs4382936, rs10898909). Among women, the distribution of the dominant rs4944832 phenotype (GG vs. GA+AA) differed significantly between the CI patients and the control 1 group (P=0.043) and between the CI patients and the control 2 group (P=0.029). Logistic regression analysis showed that the GG genotype of rs4944832 was significantly more prevalent in the female CI patients than in the control 1 (P=0.021) and control 2 groups (P=0.005). For all subjects, the overall distribution of the haplotype established by rs1783596-rs4382936-rs10898909 was significantly different between the CI patients and the control 1 group (P=0.027). For all subjects, the frequency of the T-A-G haplotype (rs1783596-rs4382936-rs10898909) was also significantly higher (P=0.031), whereas the frequency of the T-C-G haplotype (rs1783596-rs4382936-rs10898909) was significantly lower (P=0.029) in the CI patients than in the control 1 group. The present results indicate that the T-A-G haplotype of the human P2RY2 gene is a susceptibility haplotype for CI in Japanese subjects, and that the GG genotype is a genetic marker for CI, particularly in Japanese women.

Relationship between haplotypes of KCNN4 gene and susceptibility to human vascular diseases in Japanese.

BACKGROUND: Human vascular diseases such as myocardial infarction (MI) and cerebral infarction (CI) are thought to be affected by several environmental factors and genetic variants. It has been suggested that the expression of the KCNN4 calcium-activated potassium channel is associated with the developing vascular smooth-muscle cells of human neointimal hyperplasia. The aim of this study was to investigate the relationship between single-nucleotide polymorphisms (SNPs) in the human KCNN4 gene or haplotypes and the incidence of MI or CI in Japanese. MATERIAL/METHODS: Three hundred thirteen MI and 176 CI patients with 290 controls were enrolled in two independent case-control studies that examined the use of a haplotype-based case-control study involving five SNPs of the human KCNN4 gene (rs670950, rs2306801, rs2306799, rs347519, and rs3786954). RESULTS: There were significant differences between the MI and control groups in the overall distribution of genotypes and dominant or recessive models of rs670950, rs2306799, and rs3786954. Multiple logistic regression analyses revealed that even after adjusting for confounding factors (odds ratio: 1.96), the frequency of the G/G genotype of rs2306799 in the MI group was significantly higher than in the control group (p=0.005). Furthermore, the G-T-A haplotype of rs2306799-rs347519-rs3786954 was significantly more frequent in the MI (88.8%) than in the control group (83.6%). CONCLUSIONS: The specific SNPs and haplotypes in the KCNN4 gene showed significant differences between MI and control patients. These results indicate that these polymorphisms and haplotypes could be genetic markers for MI.

Haplotype-based case-control study between human apurinic/apyrimidinic endonuclease 1/redox effector factor-1 gene and cerebral infarction.

OBJECTIVES: The aim of this study was to investigate the relationship between cerebral infarction (CI) and the human apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/REF-1) gene using single-nucleotide polymorphisms (SNPs) and a haplotype-based case-control study. DESIGN AND METHODS: We selected 5 SNPs in the human APE1/REF1 gene (rs1760944, rs3136814, rs17111967, rs3136817 and rs1130409), and performed case-control studies in 177 CI patients and 309 control subjects. RESULTS: rs17111967 was found to have no heterogeneity in Japanese. The overall distribution of the haplotype-based case-control study constructed by rs1760944, rs3136814 and rs1130409 showed a significant difference. The frequency of the G-C-T haplotype was significantly higher in the CI group than in the control group (2.5% vs. 0.0%, p>0.001). CONCLUSIONS: Based on the results of the haplotype-based case-control-study, the G-C-T haplotype may be a genetic marker of CI, and the APE1/REF-1 gene may be a CI susceptibility gene.

Health literacy and physical and psychological wellbeing in Japanese adults.

OBJECTIVE: To determine the prevalence of low health literacy and investigate the relationship between low health literacy and physical and psychological wellbeing in the Japanese general population. METHODS: A web-based cross-sectional survey was conducted in a national sample of Japanese adults. Health literacy was measured by self-report using the validated single-item screening question, "How confident are you filling out forms by yourself?" Wellbeing was measured with the physical and psychological domains of the World Health Organization Quality of Life Assessment-BREF. Effect sizes were computed by dividing the mean difference in scores by the standard deviation of the scores of all participants. RESULTS: In 1040 adult enrollees (mean age, 57-year-old; women, 52%), there were 161 (15.5%; 95% confidence interval [CI], 13.3-17.7%) with low health literacy. Individuals with low health literacy reported lower physical wellbeing (60.6 vs. 71.7, p<0.001) and psychological wellbeing (59.7 vs. 68.3, p<0.001) compared with those with adequate health literacy. After adjusting for sociodemographic characteristics, health risk behaviors and chronic conditions, these differences were still significant (physical wellbeing, p<0.001; psychological wellbeing, p<0.001). The effect sizes of the difference of scores were moderate for physical wellbeing (-0.55) and also for psychological wellbeing (-0.44). CONCLUSION: The prevalence of self-reported low health literacy in Japanese adults is substantial and it is independently associated with poorer physical and mental wellbeing. PRACTICE IMPLICATIONS: Efforts to monitor health literacy and to evaluate causal pathways to poor wellbeing should be encouraged in the Japanese population.

A haplotype of the CYP4F2 gene associated with myocardial infarction in Japanese men.

This study assessed associations between the CYP4F2 gene and myocardial infarction (MI), using a haplotype-based case-control study of 234 MI patients and 248 controls genotyped for 5 single-nucleotide polymorphisms (rs3093105, rs3093135, rs1558139, rs2108622, rs3093200). For men, G allele frequency of rs2108622 and frequency of the T-C-G haplotype were significantly higher, and frequency of the T-C-A haplotype was significantly lower for MI patients than for controls (P=0.006, P=0.001 and P=0.002, respectively).

Association of extracellular superoxide dismutase gene with cerebral infarction in women: a haplotype-based case-control study.

It has been reported that oxidative stress is a factor in cerebral infarction (CI). Extracellular superoxide dismutase (EC-SOD) is important in preventing oxidative stress, and the cerebral infarct size of EC-SOD knockout mice is significantly larger than that in wild-type controls. The aim of this study was to investigate the relationship between CI and the human EC-SOD gene using single-nucleotide polymorphism (SNP) in Japanese individuals. We selected five single-nucleotide polymorphisms of the human EC-SOD gene (rs13306703, rs699473, rs17881426, rs2536512 and rs1799895) and performed a case-control study using each SNP and haplotype in 175 CI patients (103 men, 72 women) and 299 controls (144 men and 155 women). Among women, there were significant differences between the CI and control group in overall distribution of alleles for rs699473 (men: OR=1.031, 95% CI: 0.705-1.506, women: OR=1.916, 95% CI: 1.196-3.071) and rs2536512 (men: OR=0.774, 95% CI: 0.523-1.146, women: OR=2.107, 95% CI: 1.227-3.462). In a haplotype-based case control on rs13306703, rs699473 and rs1799895 in women, the frequency of the C-C-C haplotype was significantly higher in the CI group than in the control group (men; 51.5% vs 51.4% p=0.9865, women; 62.5% vs 49.7% p=0.0108). Multiple logistic regression analysis also revealed a significant difference in C-C-C haplotype in women, even after adjustment for confounding factors (OR=2.205, 95% CI: 1.069-4.552 p=0.032). The C-C-C haplotypes could be genetic markers for CI, and the EC-SOD gene may be a susceptibility gene for CI in women.