The frequency of the ΔF508 mutation on cystic fibrosis chromosomes in Israeli families: correlation to CF haplotypes in Jewish communities and Arabs

Summary We have analysed the distribution of the ΔF508 mutation and the haplotypes of cystic fibrosis (CF) bearing chromosomes among the Israeli CF population. The population was classified according to its ethnic origin and included 3 groups, Ashkenazi Jews, Sephardic/Oriental Jews and Arabs. Haplotype B (KM19 allele 2, XV2c allele 1) was found to be the predominant haplotype in all groups but in each of them the haplotype distribution was different. The ΔF508 mutation was present in all groups and accounts for 32% of the CF mutations. It was mainly associated with the B haplotype but only one third of the CF chromosomes with this haplotype carry the ΔF508 mutation. This work is dedicated to Dr. Ruth Voss who initiated the CF study in Israel and was tragically killed in a car accident on 7 August 1988     

Sex-specific effect of the thermolabile C677T mutation in the methylenetetrahydrofolate reductase gene on angiographically assessed coronary artery disease in Brazilians

Hyperhomocysteinemia is associated with increased coronary artery disease (CAD) risk. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of homocysteine and presents a common mutation (C677T) that leads to a thermolabile enzyme, mild hyperhomocysteinemia, and increased CAD risk. The C677T MTHFR mutation was studied in 772 subjects (480 Caucasian Brazilians and 292 African Brazilians) who underwent coronary angiography at the hemodynamic center of the Santa Izabel Hospital in Salvador, Bahia State, Brazil. The 677T allele frequency was increased in Caucasian Brazilians (28.1%) compared to the frequency observed in African Brazilians (18.3%; p < 0.001). In Caucasian Brazilians the frequency of the 677T homozygous genotype was increased in CAD cases (10.4%) compared to control subjects (1.4%; p = 0.014) in males but not in females. In African Brazilians the mutation was not associated with CAD in either sex. The multivariate logistic regression analysis of all the samples shows that the 677T homozygous interaction with sex was a significant CAD predictor, independent of other classical risk factors and ethnic group. The odds ratio associated with male 677T homozygotes was increased 9.2-fold (p = 0.021) compared to the 677C carriers. The present study suggests that the C677T MTHFR mutation is associated with increased CAD risk in a sex-dependent manner in Brazilians.     

The Frequent 5,10-Methylenetetrahydrofolate Reductase C677T Polymorphism Is Associated with a Common Haplotype in Whites, Japanese, and Africans

The common 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism causes decreased activity of this enzyme and can be associated with mild-to-moderate hyperhomocysteinemia in homozygotes, particularly when there is folic acid deficiency, as well as with vascular dementia, arterial thrombosis, venous thrombosis, neural-tube defects, and fetal loss. When folic acid intake is sufficient, homozygotes for MTHFR 677T appear to be protected against colon cancer and acute lymphatic leukemia, and fetuses bearing this genotype have an augmented survival. The distribution of MTHFR 677T is worldwide, but its frequency in different populations varies extensively. In the present study, we addressed the question of whether the MTHFR 677T alteration has an ancestral origin or has occurred repeatedly. We analyzed the frequency distribution of the previously described polymorphism A1298C in exon 7 and of three intronic dimorphisms, in white Israelis (Jews and Arabs), Japanese, and Ghanaian Africans. The 677T allele was, remarkably, associated with one haplotype, G-T-A-C, in white and Japanese homozygotes. Among the Africans, analysis of maximum likelihood also disclosed an association with the G-T-A-C haplotype, although none of the 174 subjects examined was homozygous for MTHFR 677T. These results suggest that the MTHFR 677T alteration occurred on a founder haplotype that may have had a selective advantage.     

Phosphoglycolate phosphatase in several population groups in Israel

The genetic polymorphism of phosphoglycolate phosphatase (PGP) found in red blood cells has been investigated in several population groups in Israel: Ashkenazi Jews, non-Ashkenazi Jews from Iraq, Yemen, Turkey, Iran, Balkan, North Africa and Arabs. The distribution of the PGP genes was not homogeneous (chi 2 = 40.545; d.f. = 20; p less than 0.005). The PGP2 gene frequency varied between 0.0185 in the Yemenite and 0.0688 in the Iranian Jews. PGP3 gene frequency ranged between 0.0062 in the Iranian and 0.0547 in the Moroccan Jews. Depsite this heterogeneity all the Israeli population groups showed some unifying characteristics which differentiated them from a random European population sample, namely higher frequencies of PGP1 gene (92-97% as opposed to 82% in th European sample) and lower frequencies of PGP2 gene (1.8-6.8% compared to 12.9% among Europeans).     

Genetic polymorphism of delta-aminolevulinate dehydrase in several population groups in Israel

The genetic polymorphism of red cell delta aminolevulinate dehydrase (ALADH) has been investigated in several population groups in Israel: Ashkenazi Jews, non-Ashkenazi Jews from North Africa, Egypt, Turkey, Iraq, Iran, Yemen and the Balkans, and Arabs. The distribution of the ALADH genes was not homogeneous (chi 2 = 36.83; d.f. = 8; p less than 0.0005). A significantly higher frequency of the ALADH2 gene was observed among the Ashkenazi Jews (0.2021) than among the non-Ashkenazi Jews and Arabs (gene frequencies 0.0825-0.1290) or all the other population samples so far studied (Liberia, Japan, Italy, Germany and Spain).     

Ethnic differences of coronary artery disease-associated SNPs in two Israeli healthy populations using MALDI-TOF mass spectrometry

Differences in prevalence and mortality from coronary artery disease (CAD) were observed among the different Israeli ethnic groups. The incidence of CAD in Israel is highest among Ashkenazi Jews and is much lower among Yemenite Jews. In this present study, we selected 15 single nucleotide polymorphisms (SNPs) from 14 candidate genes involved in (1) the renin-angiotensin system, (2) lipid metabolism, (3) cytokines and adhesion molecules, and (4) growth factors, and (5) the coagulation-fibrinolysis system. We analyzed the 15 SNPs in 94 Israeli healthy populations (47 Ashkenazi Jews and 47 Yemenite Jews) obtained from the National Laboratory for the Genetics of Israeli Populations. We applied chip-based MALDI-TOF mass spectrometry as a method for screening multiplexed genotyping of SNPs for ethnic difference in these healthy populations. Among the 15 candidate SNPs, significant differences in allelic frequency were observed in the 1166A>C of the AGTR1 gene, R158C of the Apo E gene, W64R of the ADRB3 gene, S101S of the TIMP 2 gene, and A222V of the MTHFR gene with respect to allele frequency. The incidence of A/C allele of the AGTR1 gene were 0.638/0.362 vs 0.765/0.235, C/T allele in the apo E gene was 0.915/0.085 vs 0.989/0.011, T/C allele of the ADRB3 gene was 0.989/0.0011 vs 0.926/0.074, G/A allele of the TIMP2 gene was 0.974/0.054 vs 0.830/0.170, and C/T allele in the MTHFR gene was 0.521/0.479 vs 0.819/0.181 for Ashkenazi Jews and Yemenite Jews, respectively. We demonstrated an ethnic difference of CAD-associated SNPs in two Israeli healthy populations using MALDI-TOF mass spectrometry. Further study is necessary to prove causal relation with CAD-associated SNPs and the prevalence of CAD.     

The Y chromosome pool of Jews as part of the genetic landscape of the Middle East

A sample of 526 Y chromosomes representing six Middle Eastern populations (Ashkenazi, Sephardic, and Kurdish Jews from Israel; Muslim Kurds; Muslim Arabs from Israel and the Palestinian Authority Area; and Bedouin from the Negev) was analyzed for 13 binary polymorphisms and six microsatellite loci. The investigation of the genetic relationship among three Jewish communities revealed that Kurdish and Sephardic Jews were indistinguishable from one another, whereas both differed slightly, yet significantly, from Ashkenazi Jews. The differences among Ashkenazim may be a result of low-level gene flow from European populations and/or genetic drift during isolation. Admixture between Kurdish Jews and their former Muslim host population in Kurdistan appeared to be negligible. In comparison with data available from other relevant populations in the region, Jews were found to be more closely related to groups in the north of the Fertile Crescent (Kurds, Turks, and Armenians) than to their Arab neighbors. The two haplogroups Eu 9 and Eu 10 constitute a major part of the Y chromosome pool in the analyzed sample. Our data suggest that Eu 9 originated in the northern part, and Eu 10 in the southern part of the Fertile Crescent. Genetic dating yielded estimates of the expansion of both haplogroups that cover the Neolithic period in the region. Palestinian Arabs and Bedouin differed from the other Middle Eastern populations studied here, mainly in specific high-frequency Eu 10 haplotypes not found in the non-Arab groups. These chromosomes might have been introduced through migrations from the Arabian Peninsula during the last two millennia. The present study contributes to the elucidation of the complex demographic history that shaped the present-day genetic landscape in the region.     

High-resolution Y chromosome haplotypes of Israeli and Palestinian Arabs reveal geographic substructure and substantial overlap with haplotypes of Jews

High-resolution Y chromosome haplotype analysis was performed in 143 paternally unrelated Israeli and Palestinian Moslem Arabs (I&P Arabs) by screening for 11 binary polymorphisms and six microsatellite loci. Two frequent haplotypes were found among the 83 detected: the modal haplotype of the I&P Arabs (approximately 14%) was spread throughout the region, while its one-step microsatellite neighbor, the modal haplotype of the Galilee sample (approximately 8%), was mainly restricted to the north. Geographic substructuring within the Arabs was observed in the highlands of Samaria and Judea. Y chromosome variation in the I&P Arabs was compared to that of Ashkenazi and Sephardic Jews, and to that of North Welsh individuals. At the haplogroup level, defined by the binary polymorphisms only, the Y chromosome distribution in Arabs and Jews was similar but not identical. At the haplotype level, determined by both binary and microsatellite markers, a more detailed pattern was observed. Single-step microsatellite networks of Arab and Jewish haplotypes revealed a common pool for a large portion of Y chromosomes, suggesting a relatively recent common ancestry. The two modal haplotypes in the I&P Arabs were closely related to the most frequent haplotype of Jews (the Cohen modal haplotype). However, the I&P Arab clade that includes the two Arab modal haplotypes (and makes up 32% of Arab chromosomes) is found at only very low frequency among Jews, reflecting divergence and/or admixture from other populations.     

Screening for five mutations detects 97% of cystic fibrosis (CF) chromosomes and predicts a carrier frequency of 1:29 in the Jewish Ashkenazi population.

To determine the distribution and frequency of cystic fibrosis (CF) mutations in the Israeli population, we have screened 96 patients for 11 relatively common mutations. Five mutations--delta F508, G542X, W1282X, N1303K, and 3849 + 10kb C-->T--were found to account for 97% of the CF alleles in the Ashkenazi Jews. In contrast, of the 11 mutations tested, only delta F508 was detected in Jewish patients of Sephardic or Oriental origin, accounting for 43% of the CF alleles. Four mutations--delta F508, G542X, W1282X, and N1303K--accounted for 55% of the CF alleles in Arab patients. In a pilot screening study, a random sample of 424 Ashkenazi individuals was analyzed for three mutations--delta F508, W1282X, and G542X. Thirteen individuals were detected as heterozygotes (six for delta F508 and seven for W1282X), predicting a heterozygote frequency of 1:29. This is similar to the frequency of carriers in the Caucasian population of northern European ancestry. On the basis of these data, the Ashkenazi population is considered to be a candidate for CF heterozygote screening.     

Y-chromosome DNA haplotypes in Jews: comparisons with Lebanese and Palestinians

One Y-specific DNA polymorphism (p49/Taq I) was studied in 54 Lebanese and 69 Palestinian males, and compared with the results found in 693 Jews from three communities (Oriental, Sephardic, and Ashkenazic). Lebanese, Palestinian, and Sephardic Jews seem to be similar in their Y-haplotype patterns, both with regard to the haplotype distributions and the ancestral haplotype VIII frequencies. The haplotype distribution in Oriental Jews is characterized by a significantly higher frequency of haplotype VIII. These results confirm similarities in the Y-haplotype frequencies in Lebanese, Palestinian, and Sephardic Jewish men, three Near-Eastern populations sharing a common geographic origin.     

The frequency of the C854 mutation in the aspartoacylase gene in Ashkenazi Jews in Israel.

Canavan disease (CD) is an infantile neurodegenerative disease that is transmitted in an autosomal recessive manner and has mainly been reported in Ashkenazi Jewish families. The primary enzymatic defect is aspartoacylase deficiency, and an A-to-C transition at nucleotide 854 of the cDNA has recently been reported. We screened 18 patients with CD and 879 healthy individuals, all Israeli Ashkenazi Jews, for the mutation. All 18 patients were homozygotes for the mutation, and 15 heterozygotes were found among the healthy individuals. The results disclose a carrier rate of 1:59 and suggest that a screening for the mutation is warranted among Ashkenazi Jewish couples.     

Methylenetetrahydrofolate reductase gene polymorphisms in patients with nonalcoholic steatohepatitis (NASH)

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal hepatic steatosis in the absence of a history of alcohol use. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms result in hyperhomocysteinemia. To examine whether the C677T and A1298C polymorphisms of the MTHFR gene were associated with NASH, we analysed the allele and genotype distribution of the MTHFR C677T and A1298C polymorphisms in 57 well-diagnosed NASH patients, 324 healthy controls in a case-control study of Turkish subjects of Caucasian origin. The diagnosis of the NASH patients was based on liver biopsy. The method used in the analysis of genotypes was PCR-RFLP. The MTHFR A1298C polymorphism was significantly associated with NASH (chi(2) = 8.439; p = 0.015) in the total NASH patients compared with healthy controls. The MTHFR 1298C allele (odds ratio (OR) = 2.480; 95%CI = 1.286-4.782; chi(2) = 7.703; df = 1; p = 0.006) was significantly associated with NASH in the total NASH patients. The MTHFR C677C/A1298C compound genotype (OR = 2.218; 95%CI = 1.003-4.906; chi(2) = 3.998; df = 1; p = 0.046) in men patients was also significantly associated with NASH. Likewise the MTHFR C1298C genotype was significantly associated with NASH in women patients with NASH (OR = 2.979; 95%CI = 1.027-8.641; chi(2) = 4.343; df = 1; p = 0.037). In conclusion, the MTHFR 1298C allele in all NASH patients, C1298C genotype, C677C/C1298C compound genotype in women NASH patients and C677C/A1298C compound genotype in men NASH patients were genetic risk factors for NASH.     

Ethnic differences in CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) genotypes in Japanese and Israeli populations

CYP2C9 is a major P450 2C enzyme, which hydroxylates about 16% of drugs that are in current clinical use and contributes to the metabolism of a number of clinically important substrate drugs such as warfarin. Ethnic differences in the genetic variation of CYP2C9 have been reported, and might be related to the frequencies of adverse reactions to drugs metabolized by CYP2C9 in different ethnic groups. In the present study, ethnic differences in the CYP2C9*2 and CYP2C9*3 allele distribution in Japanese and Israeli populations were evaluated using a newly developed oligonucleotide based DNA array (OligoArray(R)). The population studied consisted of 147 Japanese and 388 Israeli donors (100 Ashkenazi Jews, 99 Yemenite Jews, 100 Moroccan Jews and 89 Libyan Jews). The CYP2C9*2 [Arg144Cys (416 C>T), exon 3] and CYP2C9*3 [Ile359Leu (1061 A>C), exon 7] genotypes were determined using an OligoArray(R). The accuracy of genotyping by the OligoArray(R) was verified by the fluorescent dye-terminator cycle sequencing method. A Hardy-Weinberg test indicated equilibrium (chi(2)<3.84 is Hardy-Weinberg) in all populations. The CYP2C9*2 genotype (CC/CT+TT) was absent in Japanese (1/0) (OR 0.02), and its frequency was significant in Libyan Jews (0.697/0.303) (OR 2.13; 95% CI 1.07-4.24) compared with Ashkenazi Jews (0.83/0.17), Yemenite Jews (0.899/0.101), and Moroccan Jews (0.81/0.19). The frequencies of CYP2C9*3 genotype (AA/AC+CC) was significantly lower in Japanese (0.986/0.014) (OR 0.08), and was higher in Libyan Jews (0.652/0.348) (OR 3.03; 95% CI 1.5-6.1) and Moroccan Jews (0.77/0.23) (OR 1.69; 95% CI 0.62-3.48) compared with those in Ashkenazi Jews (0.85/0.15) and Yemenite Jews (0.849/0.151). Thus, the CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) variants were rare in the Japanese population, and showed different frequencies in the four Jewish ethnic groups examined.     

Genotype and allele frequencies of the polymorphic methylenetetrahydrofolate reductase gene in Turkey

The polymorphic methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms C677T and A1298C cause mild hyperhomocysteinemia, not only in homozygotes for C677T, but also in compound heterozygotes for C677T/A1298C. The aim of this study was to determine allelic frequencies of the polymorphic MTHFR gene C677T, A1298C. In this regard, we have investigated the allelic frequencies of C677T and A1298C polymorphisms of the MTHFR gene in 1684 randomized individuals around Turkey. DNA samples isolated from peripheral blood samples of randomized individuals were analysed. The study population consisted of 1004 females and 680 males. The frequency in Turkey of the C677T was 42.9 %; of C677C, 47.4 %; and of T677T, 9.6 %. The frequency in Turkey of A1298C was 43.7 %; of A1298A, 46.3 %; and of C1298C, 10.0 %. The allelic frequencies of the T allele of MTHFR 677 and the C allele of MTHFR 1298 were 33.34 and 33.16 %, respectively. The frequency of C677T/A1298C compound heterozygosity is highest in Turkey (21.6 %), as compared to Canada (15 %), the United States (17 %) and The Netherlands (20 %).     

A novel founder mutation in the RNASEL gene, 471delAAAG,is associated with prostate cancer in Ashkenazi Jews

HPC1/RNASEL was recently identified as a candidate gene for hereditary prostate cancer. We identified a novel founder frameshift mutation in RNASEL, 471delAAAG, in Ashkenazi Jews. The mutation frequency in the Ashkenazi population, estimated on the basis of the frequency in 150 healthy young women, was 4% (95% confidence interval [CI] 1.9%-8.4%). Among Ashkenazi Jews, the mutation frequency was higher in patients with prostate cancer (PRCA) than in elderly male control individuals (6.9% vs. 2.4%; odds ratio = 3.0; 95% CI 0.6-15.3; P=.17). 471delAAAG was not detected in the 134 non-Ashkenazi patients with PRCA and control individuals tested. The median age at PRCA diagnosis did not differ significantly between the Ashkenazi carriers and noncarriers included in our study. However, carriers received diagnoses at a significantly earlier age, compared with patients with PRCA who were registered in the Israeli National Cancer Registry (65 vs. 74.4 years, respectively; P<.001). When we examined two brothers with PRCA, we found a heterozygous 471delAAAG mutation in one and a homozygous mutation in the other. Loss of heterozygosity was demonstrated in the tumor of the heterozygous sib. Taken together, these data suggest that the 471delAAAG null mutation is associated with PRCA in Ashkenazi men. However, additional studies are required to determine whether this mutation confers increased risk for PRCA in this population.     

The molecular basis of autosomal recessive diseases among the Arabs and Druze in Israel

The Israeli population mainly includes Jews, Muslim and Christian Arabs, and Druze In the last decade, data on genetic diseases present in the population have been systematically collected and are available online in the Israeli national genetic database (). In the non-Jewish population, up to 1 July 2010, the database included molecular data on six diseases relatively frequent in the whole population: thalassemia, familial Mediterranean fever (FMF), cystic fibrosis, deafness, phenylketonuria and congenital adrenal hyperplasia, as well as data on 195 autosomal recessive diseases among Muslim Israeli Arabs, 11 among the Christian Arabs and 31 among Druze. A single mutation was characterized in 149 out of the 238 rare disorders for which the molecular basis was known. In many diseases, mutation had never been observed in any other population and was present in one family only suggesting that it occurred as a de novo event. In other diseases, the mutation was present in more than one community or even in other populations such as Bedouins from the Arab peninsula or Christians from Lebanon. In the 89 other disorders, more than one mutation was characterized either in the same gene or in more than one gene. While it is probable that most of these cases represent random events in some cases such as Bardet Biedl among the Bedouins, the reason may be a selective advantage to the heterozygotes.     

亚甲基四氢叶酸还原酶基因C677T、G1793A 单核苷酸多态性 与散发性乳腺癌易感性的关系

目的:研究亚甲基四氢叶酸还原酶(MTHFR)基因C677T、G1793A位点单核苷酸多态性与散发性乳腺癌易感性关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,对200例乳腺癌患者及200例正常对照者MTHFR基因C677T、G1793A位点单核苷酸多态性进行分析,logistic回归分析不同基因型与乳腺癌风险的关系。结果:乳腺癌组MTHFR 677TT基因型频率为25.00%显著高于正常对照组的10.50%(X2=14.401,P=0.001),CT基因型频率为44.50%低于正常对照组的54.50%,CC基因型频率在乳腺癌组和正常对照组中无差别;MTHFR 1793GA基因型频率为18.50%显著高于正常对照者的8.50%(X2=8.563,P=0.003)。乳腺癌患者MTHFR 677T和1793A等位基因频率分别为47.25%、9.25%,显著高于对照组中的37.75%、4.25%。MTHFR 677TT基因型携带者罹患乳腺癌的风险是677CC基因型携带者的2.732倍(95%CI=1.418～5.051,P=0.001),MTHFR1793GA基因型携带者罹患乳腺癌的风险是1793GG基因型携带者的2.444倍(95%CI=1.325～4.505,P=0.003)。另外,乳腺癌组中MTHFR C677T基因多态性与肿瘤大小相关(x2=7.431,P=0.024,MTHFR G1793A基因多态性与淋巴结转移情况(x2=8.939,P=0.011)、癌组织学分级(x2=9.983,P=0.007)相关。结论:MTHFR C677T、G1793A基因多态性与散发性乳腺癌的易感性相关。     

Genotypic Differences of Candida albicans and C. dubliniensis Isolates Related to Ethnic/Racial Differences within the Same Geographic Area

Candida albicans and C. dubliniensis genotype differences among Israeli ethnic groups were assessed. Isolates from Jews (51), Arabs (35) and Druze (25) were genotyped. The distributions among ethnic groups were not different, however they differed (p = 0.002) from global populations. Therefore, C. albicans and C. dubliniensis genotype distribution differences in Israel are related to changes in all ethnic groups.     

Study of the mutation M694V of familial Mediterranean fever in Jews

Familial Mediterranean fever (FMF) is a recessively inherited disorder characterized by episodes of fever with abdominal pain, pleurisy, or arthritis. The familial Mediterranean fever gene, designated MEFV, was recently cloned, and the missense mutation M694V accounting for most of the patients with this disease was identified. The objective of the present study was to establish frequencies of the M694V mutation in three groups of Jews. The subjects studied were 381 Sephardi, 256 Ashkenazi, and 65 Oriental Jews, all male subjects, previously collected for an anthropological study, independent of their FMF status. The M694V mutation in the 702 samples was assessed by amplifying genomic DNA with the use of primers that selectively amplify the normal or altered DNA sequence of the M694V mutation, by the amplification refractory mutation system (ARMS). In our sample of Sephardi Jews, the frequency of the M694V mutation is elevated (10.9%), and this is also the case for Oriental Jews (9.2%). In our sample of Ashkenazis, the M694V allele frequency is very low (0.8%).     

亚甲基四氢叶酸还原酶基因C677T、G1793A单核苷酸多态性与散发性乳腺癌易感性的关系

目的：研究亚甲基四氢叶酸还原酶（MTHFR）基因C677T、G1793A位点单核苷酸多态性与散发性乳腺癌易感性关系。方法：采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法,对200例乳腺癌患者及200例正常对照者MTHFR基因C677T、G1793A位点单核苷酸多态性进行分析,logistic回归分析不同基因型与乳腺癌风险的关系。结果：乳腺癌组MTHFR 677TT基因型频率为25.00%显著高于正常对照组的10.50%（X2=14.401,P=0.001）,CT基因型频率为44.50%低于正常对照组的54.50%,CC基因型频率在乳腺癌组和正常对照组中无差别;MTHFR 1793GA基因型频率为18.50%显著高于正常对照者的8.50%（X2=8.563,P=0.003）。乳腺癌患者MTHFR 677T和1793A等位基因频率分别为47.25%、9.25%,显著高于对照组中的37.75%、4.25%。MTHFR 677TT基因型携带者罹患乳腺癌的风险是677CC基因型携带者的2.732倍（95%CI=1.418～5.051,P=0.001）,MTHFR1793GA基因型携带者罹患乳腺癌的风险是1793GG基因型携带者的2.444倍（95%CI=1.325～4.505,P=0.003）。另外,乳腺癌组中MTHFR C677T基因多态性与肿瘤大小相关（x2=7.431,P=0.024,MTHFR G1793A基因多态性与淋巴结转移情况（x2=8.939,P=0.011）、癌组织学分级（x2=9.983,P=0.007）相关。结论：MTHFR C677T、G1793A基因多态性与散发性乳腺癌的易感性相关。