Equal proportion of adult male and female homozygous for the 677C --> T mutation in the methylenetetrahydrofolate reductase polymorphism.
Equal proportion of adult male and female homozygous for the 677C --> T mutation in the methylenetetrahydrofolate reductase polymorphism.
复制标题
亚甲基四氢叶酸还原酶多态性中 677C --> T 突变的成年男性和女性纯合子比例相等。
DOI：
10.1002/ajmg.a.30391
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Motulsky,ArnoG
中科院分区：
文献类型：
--
作者：
Anderson,CherylAM;Jorgensen,ArneLund;Deeb,Samir;McLerran,Dale;Beresford,ShirleyAA;Motulsky,ArnoG
Evidence suggests that a polymorphism of the autosomal gene encoding for 5, 10 methylenetetrahydrofolate reductase (MTHFR)[Frosst et al., 1995] gives rise to a thermolabile form [Kang et al., 1988] of the enzyme that in the homozygous state is associated with increased levels of homocysteine under conditions of less than optimal folate nutrition [Jacques et al., 1996]. This polymorphism is due to a C→ T substitution at nucleotide 677 which converts an alanine to valine in a conserved portion of the molecule [Frosst et al., 1995] and appears to be a risk factor for increased plasma levels of homocysteine and vascular diseases [Boushey et al., 1995; Jacques et al., 1996; Kluijtmans et al., 1997]. In a 1999 letter to the Editor of the American Journal of Medical Genetics, Rima Rozen et al. presented data examining the frequencies of the three methylenetetrahydrofolate reductase (MTHFR) genotypes in newborn healthy infants ascertained by the California Birth Defects Monitoring Program [Rozen and Shaw, 1999]. It was suggested that homozygosity for the common 677 C→ T mutation in MTHFR gene was more frequent among newborn males than among newborn females. The apparent gender difference was observed among 915 newborn infants used as control populations in studies of an association between the MTHFR polymorphism and neural tube defects. Rozen and Shaw [1999] stratified this group of 915 newborn control healthy infants by MTHFR genotypes and found that among 150 infants who had the TT variant for MTHFR only 50 (33%) were female. This was significantly less (P< 0.01) than the expected 50% of female infants. We examined the frequencies of the threeMTHFR genotypes in 559 healthy, Caucasian, male and female adult volunteers from Seattle, WA for a controlled intervention study of homocysteine response to folic acid supplementation with variable dosage. As shown in Table I, and similar to the findings of Rozen and Shaw [1999], we detected a significantly lower proportion of females than males to be homozygous for the 677C→ T mutation in MTHFR. Among the 173 males and 386 females analyzed, we found 13.9% of male volunteers were TT homozygotes in comparison to 7.8% of female volunteers (Chi square: P< 0.05). We also found that the T allele relative frequency is significantly different between males and females (P= 0.02). These results suggest some variation in our data in the MTHFR genotypes due to gender. We hypothesized that there may be two possible reasons for the observed reduction in frequency of MTHFR TT homozygotes in females. The first is a possible prenatal selection against TT female homozygotes, and the second is a possible higher T allele frequency in males than females.To explore the observed reduction in frequency of MTHFR TT homozygotes in females, we conducted a literature search for studies specifying MTHFR genotypes and gender for healthy adult individuals, typically from population and case-control studies. We assumed that a sex difference observed at birth would survive into adulthood since we know of no postnatal condition associated with the MTHFR polymorphism that would eliminate such differences during childhood. The keywords used to produce a primary list in the PubMed literature search were MTHFR, gender, and sex. Two articles were carefully reviewed for related articles [Slattery et al., 1999; Ulrich et al., 2000]. From this search, the list of articles in Table II was generated and was considered representative of the literature on the subject [Adams et al., 1996; Brugada and Marian, 1997; Christensen et al., 1997; Galinsky et al., 1997; Heijmans et al., 1999 …
