Polymorphism of the Apolipoprotein E Gene and Risk of Myocardial Infarction

The apolipoprotein E (ApoE) gene polymorphism resulting from nucleotide substitutions in exon 4 was analyzed in Russian and Tatar patients with myocardial infarction (MI) from Bashkortostan. Alleles 2, 3, and 4 were identified by PCR. The genotype frequency distribution proved to be age-dependent in healthy Russians, genotype 2/3 increasing in frequency in subjects over 45. Russians who suffered MI under 45 had lower frequencies of genotype E3/3 (50.00% vs. 75.47% in controls of the same age, = 0.013, OR = 0.33) and allele 3 (72.12% vs. 85.85%, = 0.020, OR = 0.43) and a higher frequency of allele 4 (22.12% vs. 10.38%, = 0.030, OR = 2.45). Russians who suffered MI complicated by cardiogenic shock (CS) had a significantly higher frequency of genotype 3/4 and lower frequencies of genotype 3/3 and allele 3 as compared with MI patients without CS. In Tatars, genotype 4/4 occurred at a frequency of 14.29% in patients who suffered MI under 45, and was not detected in healthy subjects of the same age ( = 0.024, OR = 17.85). Thus, the ApoE polymorphism was associated with higher risk of MI in Russians and Tatars under 45.     

Genotypes of the vitamin D-binding protein gene in patients with chronic obstructive pulmonary disease and in the healthy population of the Republic Bashkortostan

Allele and genotype frequency distributions of the vitamin D-binding protein gene (DBP) were studied in patients with chronic obstructive pulmonary disease (COPD, N = 298) and healthy individuals (N = 237) from two ethnic groups (Tatars and Russians) resident in the Republic Bashkortostan. The DBP genotype frequency distribution significantly differed between Tatars and Russians (X ² = 8.854, df = 5, P = 0.04). The DBP allele frequency distribution was similar in healthy subjects of both ethnic groups, with allele frequency decreasing as GC*1S > GC*1F > GC*2. The most common DBP genotype was GC*1F/1S in Tatars (36.79%) and GC*1S/2 in Russians (34.62%). It was demonstrated that, in Tatars, the genotype GC*1F/1S is protective against COPD, its frequency being significantly lower in COPD patients than in healthy subjects (19.85% vs. 36.79%; X ² = 7.622, P = 0.0067, P _cor = 0.0335; OR = 0.42, 95%CI 0.42–0.95). On the other hand, the genotype GC*1F/2 was more common among COPD patients than among healthy individuals (19.08% vs. 8.49%; X ² = 4.52, P = 0.033, P _cor = 0.165; OR = 2.54, 95%CI 1.067–6.20). No differences in DBP genotype and allele frequency distributions was found between COPD patients and healthy individuals in the Russian population.     

Association of the T174M Polymorphism of the Angiotensinogen Gene with Essential Hypertension in Russians and Tatars from Bashkortostan

The alleles and genotypes of the T174M polymorphism of the angiotensinogen gene were PCR-analyzed in Russians and Tatars from Bashkortostan. The genotype frequency distribution observed in either ethnic group did not differ from that reported for other populations. The T174M polymorphism was tested for association with essential hypertension (EH). Genotypes TT, TM, and MM were found respectively in 82.56, 13.95, and 3.49% normotensive Russians and in 83.81, 16.19, and 0% normotensive Tatars. The frequency of genotype TM in patients with EH onset beyond 45 years of age was significantly higher than in controls of the same age without signs of cardiovascular disorders (51.72 vs. 11.11% in Russians and 45.45 vs. 16% in Tatars). Patients with EH onset under 45 did not differ in genotype frequency distribution from normotensive subjects of the same age. Genotype TM was associated with higher risk of EH in people over 45.     

Association of the T174M polymorphism of the angiotensinogen gene with essential hypertension in Russians and Tatars from Bashkortostan

The alleles and genotypes of the T174M polymorphism of the angiotensinogen gene were PCR-analyzed in Russians and Tatars from Bashkortostan. The genotype frequency distribution observed in either ethnic group did not differ from that reported for other populations. The T174M polymorphism was tested for association with essential hypertension (EH). Genotypes TT, TM, and MM were found respectively in 82.56, 13.95, and 3.49% normotensive Russians and in 83.81, 16.19, and 0% normotensive Tatars. The frequency of genotype TM in patients with EH onset beyond 45 years of age was significantly higher than in controls of the same age without signs of cardiovascular disorders (51.72 vs. 11.11% in Russians and 45.45 vs. 16% in Tatars). Patients with EH onset under 45 did not differ in genotype frequency distribution from normotensive subjects of the same age. Genotype TM was associated with higher risk of EH in people aged beyond 45.     

Genotypes of vitamin-D-binding protein (DBP) in patients with chronic obstructive pulmonary disease and healthy population of Republic Bashkortostan

The distribution of alleles and genotypes of vitamin D-binding protein (DBP) gene has been studied in patients with Chronic Obstructive Pulmonary Disease (COPD, n = 298) and healthy individuals (n = 237) from two ethnic groups (Tatars and Russians) living in Republic Bashkortostan. Statistically significant differences in the distribution of DBP gene genotypes between Tatars and Russians (chi2 = 8.854, df = 5, P = 0.04) were revealed. The pattern of allele's distribution within DBP gene was similar in healthy control subjects of both ethnic groups, with gradient reduction in row GC*1S> GC*1F> GC*2. The most common genotypes were: GC*1F/1S in Tatars (36.79%) and GC*1S/2 in Russians (34.62%). It has been shown, that Tatars with genotype GC*1F/1S have a lower risk of COPD development: the frequency of GC*1F/1S genotype in COPD patients was significantly lower than in healthy individuals (19.85% versus 36.79%; chi2 = 7.622, P = 0.0067, Pcor = 0.0335; OR = 0.42 CI 95% 0.22-0.79). At the same time, COPD patients from the same group had higher frequency of GC* 1F/2 genotype than healthy individuals (19.08% versus 8.49%; chi2 = 4.52, P = 0.033, Pcor = 0.165; OR = 2.54 CI 95% 1.067-6.20). In Russian population the distribution of alleles and genotypes of DBP gene were similar in COPD patients and healthy individuals.     

Genetic association between the apolipoprotein E (ApoE) gene alleles and various forms of Alzheimer's disease]

Allele epsilon 4 of the apolipoprotein E (APOE) gene is associated with higher risk of Alzheimer's disease (AD) in many, though not all, ethnic groups. The APOE allele and genotype frequency distributions were studied in 207 AD patients without cerebrovascular disorders, 62 AD patients with cerebrovascular disorders (combined AD), and 206 control individuals (ethnic Russians from the Russian population). The frequency of allele epsilon 4 in patients with early-onset and late-onset AD was three times higher than in control individuals (p < 0.000001). Compared with control people, patients with cerebrovascular disorders displayed a twofold higher frequency of allele epsilon 4; the difference between the two groups was significant (p = 0.0019). Relative risk of AD in carriers of allele epsilon 4 was five times higher than in carriers of alleles epsilon 2 and epsilon 3 (p < 0.000001). Allele epsilon 2 had a protective effect with respect to AD onset until 65 years of age (p = 0.015). Thus, APOE allele epsilon 4 proved to be a universal factor of early-onset, late-onset, and combined AD in ethnic Russians from Russia.     

HindIII polymorphism of lipoprotein lipase gene and risk of myocardial infarction

The purpose of this study was to determine whether HindIII restriction polymorphism found in intron 8 of lipoprotein lipase gene is associated with the onset of myocardial infarction (MI) in Russians and Tartars living in Bashkortostan. HindIII polymorphism was investigated by the polymerase chain reaction in myocardial infarction survivors (males aged under 55 years (98 Russians and 68 Tartars) and in controls (53 Russians and 80 Tartars). The distribution of genotypes and allele frequencies in the controls were as follows: the frequencies of genotypes HindIII(-/-), HindIII(+/-), and HindIII(+/+) in Russians (3.77, 49.06, and 47.17%, respectively) did not differ from those in Tartars (7.50, 51.24, and 41.25%, respectively), while the frequency of HindIII(-) allele was 28.30% in Russians and 33.13% in Tartars. Among Tartars, the HindIII(+/+) genotype was more common in myocardial infarction survivors than in controls (OR 2.03). In the Russians this genotype was not associated with the risk of MI. The frequencies of HindIII(+/+) genotype and allele HindIII(+) were significantly higher (OR 8.96 and 6.71, respectively) and frequencies of HindIII(+/-) genotype and allele HindIII(-) were lower (OR 0.13 and 0.15) in Russian patients with repeated MI. These findings indicate that HindIII polymorphism may be a genetic risk factor for MI before 55 years of age in the Tartars and for repeated MI in Russians. This association prompts genotyping of HindIII polymorphism for predicting MI recurrence in Russian survivors after MI.     

Is the ApoE polymorphism associated with dilated cardiomyopathy?

Apolipoprotein E (ApoE) is 34 kDa protein involved in the modulation of cholesterol transport and homeostasis. Polymorphism of the ApoE gene has been implicated in many chronic cardiovascular and neuronal diseases. ApoE epsilon4 allele has been reported to be associated with increased risk of cardiovascular diseases such as myocardial infarction, hypertension, coronary heart disease, etc. Fifty patients with the end-stage dilated cardiomyopathy (DCM) and advanced congestive heart failure were examined in our study. For evaluation of ApoE polymorphism, novel approach of fast screening of ApoE gene polymorphism by combination of PCR and blotting (CVD StripAssay) was used. Individual genotypes were correlated with basic cardiologic clinical parameters. The reported frequency of this allele in Caucasian population is 14.7 %. Our results showed that in patients with DCM frequency of the ApoE epsilon4 allele is 40 %. Frequency of the genotype epsilon2/4 was 58 % and epsilon3/4 was 22 %. Comparison with control Caucasian groups monitored by others clearly revealed that frequency of epsilon4 alelle is increased in patients with advanced stages of DCM. This observation suggests association of ApoE polymorphism with severe form of DCM. Physiological consequences of this observation remain to be clarified.     

Analysis of insertion-deletion polymorphism in serotonin transporter gene in men of different ethnic appurtenance with acute alcoholic psychosis

Analysis of insertion-deletion polymorphism of serotonin vector gene (SLC6A4) was carried out in Russian and Tatar men with acute alcoholic psychosis. Significant interpopulation differences in the distribution of SLC6A4 genotype and allele frequencies were revealed. A relationship of L/S gene with the disease was detected in Russians and Tatars, but the presence of heterozygotic genotype was associated with early onset of chronic alcoholization and development of acute alcoholic psychosis in Tatars and with later alcoholization and disease development in Russians. The share of S/S genotype was significantly decreased in Russian patients aged over 35 years, which suggests selection aimed at elimination of short allele homozygotes among patients with this disease and probably different genetic prerequisites for early and late development of the disease in Russians. In Tatars aged over 35 years acute alcoholic psychosis is associated with L/L genotype (RR-3).     

Endothelial nitric oxide synthase gene minisatellite polymorphism: study in populations of the Volga-Ural region and analysis of associations with myocardial infarct and essential hypertension]

The 27-bp tandem repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene (eNOS) in populations of the Volga-Ural region was studied by means of polymerase chain reaction. In Russians and Tatars, the possible association of this polymorphism with coronary heart disease complicated by either myocaridal infarction or by essential hypertension was examined. Russians with essential hypertension associated with hypertrophy of the left ventricle displayed a statistically significant increase of the eNOS4A/B genotype and the A allele frequencies along with the decrease of the frequencies of the eNOS4B/B genotype and the B allele. In Tatars survived from myocardial infarction and with the risk of cardiovascular diseases (smoking or burdened heredity), a statistically significant increase of the frequencies of the eNOS4A/B genotype and the A allele was observed. Thus, in Russians the eNOS4A/B genotype was associated with the development of essential hypertension, while in Tatars it was associated with the risk of myocardial infarction.     

Association of cytochrome P450 genes polymorphisms (CYP1A1 and CYP1A2) with the development of chronic obstructive pulmonary disease in Bashkortostan

To assess the role that polymorphisms of cytochrome P450 genes play in genetic predisposition to chronic obstructive pulmonary disease (COPD), the allele and genotype distributions of CYPIA1 (2455 A/G, 3801T/C) and CYP1A2 (-2464T/delT, -163C/A) genes were studied in Tatar and Russian COPD patients and in cases of healthy individuals (Russian, Tatar and Bashkir), residents of Bashkortostan. It was shown that the CYP1A1 and CYP1A2 genes haplotypes frequency distribution patterns do not differed between Tatars and Russians ethnic groups (chi2 = 0.973, df = 3, p = 1.00 and chi2 = 1.546, df = 3, p = 0.92, respectively). Analysis of the the CYP1A1 and CYP1A2 genes haplotypes revealed statistically significant differences in the haplotypes frequency distributions between Bashkirs versus Russians and Tatars (chi2 = 12.328, df= 3,p = 0.008; chi2 = 9.218, df=3, p = 0.034, respectively for CYP1A1 gene and (chi2 = 18.779, df=3, p = 0.0001, chi = 14.326, df=3, p = 0.003, respectively for CYP1A2 gene). The (-2467)delT allele and CYP1A2*1D haplotype of CYPIA2 gene was associated with higher risk of COPD in Tatar ethnic group (OR = 1.83, 95% CI 1.24-2.71, chi2 = 9.48, p = 0.003 and chi2 = 9.733, p = 0.0027, Pcor = 0.008; OR = 3.908, 95% CI 1.56-10.19, respectively). On the other hand the CYP1A2*1A haplotype had protective effect (chi2 = 6.319, p = 0.0127, Pcor = 0.038; OR = 0.6012, 95% CI 0.402-0.898). But at the same time we did not find any differences in the genotypes and haplotypes frequency distributions of the CYP1A2 gene within the patients and healthy groups in Russian ethnic group. We also did not find any association of CYP1A1 gene with COPD in ethnic groups of Bashkortostan.     

Apolipoprotein E gene polymorphism,hypercholesterolemia and glomerular filtration rate in type 2 diabetic subjects: A 9-year follow-up study

OBJECTIVE: To study the association between apolipoprotein E (apoE) genotype and the rate of decline in glomerular filtration rate (GFR) in type 2 diabetic patients in a 9-year prospective study. METHODS: GFR was determined in 84 type 2 diabetic patients by plasma clearance of (51)Cr-EDTA at baseline and after 9 years of follow-up. ApoE genotypes were determined by polymerase chain reaction and restriction enzyme HHAI digestion and designated as epsilon4 allele group (apoE4/2, 4/3 and 4/4 genotypes; n = 20) and non-epsilon4 allele group (apoE3/3 and E3/2 genotypes; n = 64). We focused our analysis on those patients who were more likely to progress to diabetic renal disease, i.e. whose GFR fell more than expected in the normal course of ageing [1 ml x min(-1) x (1.73 m(2))(-1) per year]. RESULTS: In the whole population, the decline in the GFR did not differ statistically significantly between the apoE genotype groups [p = 0.65 with analysis of variance for repeated variables (RANOVA) for interaction between apoE genotype group and time point]. However, among patients whose GFR changed more than 9 ml x min(-1) x (1.73 m(2))(-1), GFR showed a statistically significantly greater decline in the epsilon4 allele group (n = 11) than in the non-epsilon4 allele group (n = 43) [from 116 +/- 36 to 80 +/- 29 ml x min(-1) x (1.73 m(2))(-1) vs. from 119 +/- 20 to 96 +/- 18 ml x min(-1) x (1.73 m(2))(-1); p = 0.005 with RANOVA]. CONCLUSION: ApoE allele epsilon4 may speed up the rate of decline of the GFR in patients with progressive diabetic renal disease.     

Endothelial Nitric Oxide Synthase Gene Minisatellite Polymorphism in Populations of the Volga–Ural Region and Analysis of Its Association with Myocardial Infarction and Essential Hypertension

The 27-bp tandem repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene (eNOS) in populations of the Volga–Ural region was studied by means of polymerase chain reaction. In Russians and Tatars, the possible association of this polymorphism with coronary heart disease complicated by either myocardial infarction or by essential hypertension was examined. Russians with essential hypertension associated with hypertrophy of the left ventricle displayed a statistically significant increase of the eNOS4A/Bgenotype and theAallele frequencies along with the decrease of the frequencies of the eNOS4B/Bgenotype and the Ballele. In Tatars survived from myocardial infarction and with the risk of cardiovascular diseases (smoking or burdened heredity), a statistically significant increase of the frequencies of the eNOS4A/Bgenotype and the Aallele was observed. Thus, in Russians the eNOS4A/Bgenotype was associated with the development of essential hypertension, while in Tatars it was associated with the risk of myocardial infarction.     

M31R and R335C polymorphic variants of the IL8RA gene in Russian and Buryat patients with atopic bronchial asthma

To test the M31R and R335C polymorphisms of the Il8RA gene for association with atopic bronchial asthma (BA), the allele and genotype frequency distributions of the polymorphisms were studied in Russian patients from Moscow and Buryat patients from Ulan-Ude. The study involved two Russian groups, one including 291 DNA samples of patients with atopic BA, and the other, 266 DNA samples of healthy people. The two Buryat groups included 124 and 152 DNA samples from patients with atopic BA and healthy people, respectively. The M31R polymorphism proved to be associated with atopic BA in Russians. Allele Arg and genotype Met/Arg suggested a higher risk of BA (OR= 4.45, P = 0.003 and OR = 4.58, P = 0.003, respectively), while allele Met and genotype Met/Metwere associated with a lower risk (OR = 0.22, P = 0.003 and OR = 0.22, P = 0.003, respectively). The R335C polymorphism was not associated with atopic BA in Russians and was in Buryats. Allele Arg and homozygous genotype Arg/Arg suggested a higher risk of the disease (OR = 3.06, P = 0.030 and OR = 3.20, P = 0.027, respectively), while allele Cys and genotype Arg/Cys suggested a lower risk (OR = 0.33, P = 0.030 and OR = 0.31, P = 0.027, respectively). The results support the role of the IL8RA gene in atopic BA.     

Association of polymorphisms of the CYP1A1 and CYP1A2 cytochrome P450 genes with chronic obstructive pulmonary disease in Bashkortostan

The frequencies of polymorphisms of CYP1A1 (2455A/G, 3801T/C) and CYP1A2 (?2464T/delT, ?163C/A) were determined in healthy residents of Bashkortostan (Russians, Tatars, and Bashkirs) and tested for association with chronic obstructive pulmonary disease (COPD). Interethnic differences in the frequency distribution of the CYP1A1 and CYP1A2 polymorphisms were significant. In Tatars and Russians, the CYP1A1 and CYP1A2 haplotype frequencies were similar (χ² = 0.973, df = 3, P = 1.00 and χ² = 1.546, df = 3, P = 0.92, respectively). In Bashkirs, the CYP1A1 haplotype frequencies significantly differed from those in Russians and Tatars (χ² = 12.328, df = 3, P = 0.008 and χ² = 9.218, df = 3, P = 0.034, respectively) owing to a high frequency of CYP1A1*2B (10.17%). Similarly, Bashkirs differed from Russians and Tatars in the CYP1A2 haplotype frequencies (χ² = 18.779, df = 3, P = 0.0001 and χ² = 14.326, df = 3, P = 0.003, respectively). The frequency of the CYP1A2*1D haplotype in Bashkirs was 11.02% in contrast to 2.36% in Tatars and 1.61% in Russians. Allele *D of the CYP1A2 ?2467delT polymorphism was associated with COPD in Tatars (OR = 1.83, 95%CI 1.24–2.71, χ² = 9.48, P = 0.003). CYP1A2*1D was associated with an increased risk of COPD (8.65% vs. 2.36% in controls, χ² = 9.733, P = 0.0027, P _cor = 0.008, OR = 3.908, 95%CI 1.56–10.19). Haplotype CYP1A2*1A was significantly less frequent in patients with COPD (21.05% vs. 30.74%, χ² = 6.319, P = 0.0127, P _cor = 0.038, OR = 0.6012, 95%CI 0.402–0.898). The CYP1A1 polymorphisms were not associated with COPD in residents of Bashkortostan.     

Coenzyme Q, Vitamin E and Apo-E alleles in Alzheimer Disease

Neurodegenerative Diseases represent the most common cause of Dementia, about 5-10% of the population aged above 65 years and about 30% above 80 years. A study about Apo-E alleles, Coenzyme Q and Vitamins E as biological indicators was performed in plasma samples of patients aged from 30 to 85 years, affected by Neurodegenerative Diseases. The results were compared with control subjects of approximately the same ages as the reference group. A frequency of 21.7% of epsilon4 allele in control group was estimated, against 15.8% observed in patients. The frequency of epsilon2 and epsilon3 alleles was 13.0% and 65.2% in the control group against 10.5% and 73.7% in patients. No significant differences were observed between the frequency of epsilon3/epsilon3 genotype and epsilon3/epsilon4 genotype in the control group compared to patients' group. The frequencies observed in epsilon2/epsilon3 genotype groups were 8.7% vs 15.8% and of e2/e4 genotype 17.4% vs 5.3%. The epsilon2/epsilon2 and epsilon4/epsilon4 genotypes were not identified in any groups. Plasma CoQ10 concentrations were similar in patient and control groups and no differences were found even taking into account the distribution of male and female subjects in the two groups. Also, vitamin E did not provide evidence of any differences between groups and the analysis among sexes revealed that again vitamin E concentrations were similar in between subgroups.     

LRP-associated protein gene (LRPAP1) and susceptibility to degenerative dementia

Difference in genetic makeup of lipid metabolizing proteins may increase susceptibility to dementia. The aim of this study was to investigate variations in two lipid metabolizing genes, low-density lipoprotein receptor-related protein-associated protein gene (LRPAP) and apolipoprotein E (APOE), in vascular and degenerative dementias. This hospital-based association study included 147 patients with dementia and 163 age-matched controls. Genotyping for LRPAP1 intron 5 insertion/deletion and APOEHhaI polymorphism was carried out by polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism method. The frequency of DD genotype and *D allele of LRPAP gene was high in degenerative dementias compared with controls (76.6% vs. 44.8% and 86.4% vs. 69.3%, respectively) suggesting increased susceptibility [P < 0.0001, odds ratio (OR) =3.76 for DD genotype and P < 0.0001, OR = 2.80 for D allele]. Vascular dementia patients showed statistically insignificant but increasing trend for allele I (40.0% vs. 30.7%). We also observed significant association of APOEepsilon4 allele with degenerative dementias (P < 0.0001, OR =5.35). Our study suggests that LRPAP1-D and APOE E4 alleles significantly increase the susceptibility to degenerative dementias.     

Polymorphic gene markers of lipid metabolism are associated with diabetic nephropathy in patients with type 1 diabetes mellitus

In groups of type 1 diabetes mellitus patients with and without clinical signs of diabetic nephropathy (n = 62 and n = 68, respectively), a search was made for associations between diabetic nephropathy and the polymorphic marker epsilon2/epsilon3/epsilon4 of apolipoprotein E gene (APOE), I/D marker of apolipoprotein B gene (APOB), and Ser447Ter marker of lipoprotein lipase-encoding gene (LPL). The risk of diabetic nephropathy was higher in the carriers of allele epsilon3 and genotype epsilon3/epsilon3 of the polymorphic marker epsilon2/epsilon3/epsilon4 of APOE gene as well as in the carriers of allele 1 and APOB genotype/gene (OR = 2.08 and 2.16; 1.91 and 2.11, respectively). Conversely, the carriers of allele D showed a reduced risk of this complication (OR = 0.52). No significant differences in distribution of alleles and genotypes of the polymorphic marker Ser447Ter of LPL gene were found between the groups. Our results indicate that the genes encoding two major components of lipid metabolism are involved in the development of diabetic nephropathy in patients with type 1 diabetes mellitus.     

Association of polymorphic markers of lipid metabolism genes with diabetic polyneuropathy in type 1 diabetes mellitus

The aim of this study was the search of association with diabetic polyneuropathy of the polymorphic markers epsilon2/epsilon3/epsilon4 of apolipoprotein E (APOE) and I/D of apolipoprotein B (APOB) genes in groups of type 1 diabetes patients with diabetic polyneuropathy (n = 86) and without its clinical signs (n = 94). We have not found significant association with diabetic polyneuropathy (DPN) of epsilon2/epsilon3/epsilon4 marker of APOE gene. However the comparison of allele and genotype frequencies of I/D marker of APOB gene showed that the carriers of I allele and II genotype had higher risk (OR = 1.66 and 2.01, relatively; p < 0.027), whereas the carriers of D allele had lower risk of DPN (OR = 0.60; p < 0.018). Our findings show that APOB gene, encoding one of the main components of lipid metabolism system, is involved into the diabetic polyneuropathy development in type 1 diabetes mellitus.     

Apolipoprotein E: risk factor for Alzheimer disease.

The apolipoprotein E gene (APOE) has three common alleles (epsilon 2, epsilon 3, and epsilon 4) that determine six genotypes in the general population. In this study, we examined 77 patients with late-onset Alzheimer disease (AD), along with an equal number of age- and sex-matched controls, for an association with the APOE-epsilon 4 allele. We show that the frequency of this allele among AD patients was significantly higher than that among the control population (.351 vs. .130, P = .000006). The genotype frequencies also differed between the two groups (P = .0002), with the APOE-epsilon 4/epsilon 3 genotype being the most common in the AD group and the APOE-epsilon 3/epsilon 3 being the most common in the control group. In the AD group, homozygosity for epsilon 4 was found in nine individuals, whereas none was found in the control group. The odds ratio for AD, when associated with one or two epsilon 4 alleles, was 4.6 (95% confidence interval [CI] 1.9-12.3), while the odds ratio for AD, when associated with heterozygosity for APOE-epsilon 4, was 3.6 (95% CI 1.5-9.8). Finally, the median age at onset among the AD patients decreased from 83 to 78 to 74 years as the number of APOE-epsilon 4 alleles increased from 0 to 1 to 2, respectively (test for trend, P = .001). Our data, which are in agreement with recent reports, suggest that the APOE-epsilon 4 allele is associated with AD and that this allelic variant may be an important risk factor for susceptibility to AD in the general population.