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ORIGINAL ARTICLE  
Year : 2012  |  Volume : 5  |  Issue : 1  |  Page : 52-56
 

MTHFR C677T polymorphism is associated with hyperlipidemia in women with polycystic ovary syndrome


1 Department of Obstetrics and Gynaecology, IMS, BHU, Varanasi, India
2 Department of Medicine, IMS, BHU, Varanasi, India

Date of Submission04-Aug-2011
Date of Decision13-Oct-2011
Date of Acceptance07-Mar-2012
Date of Web Publication2-Jul-2012

Correspondence Address:
Madhu Jain
11, Lal Bhadur Shastri Colony, Karaundi Chauraha, Varanasi - 221005
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-1208.97802

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   Abstract 

Context: Women with polycystic ovary syndrome (PCOS) are prone for coronary artery disease (CAD), and hyperhomocysteinemia is an independent risk factor for CAD. MTHFR deficiency is the most common cause of hyperhomocysteinemia, thereby provoking a possible association between PCOS and MTHFR C677T polymorphism. AIMS: The aim of this study was to investigate an association of MTHFR C677T polymorphism with PCOS. Settings and Design: 92 women with PCOS (Rotterdam criteria) and 95 age-matched controls were compared with respect to MTHFR C677T polymorphism. The 2 genotypes (CC and CT) obtained were compared with clinical and laboratory parameters in women with PCOS. Materials and Methods: In a case-control study, clinical, biochemical, hormonal and genetic analysis (PCR-RFLP of peripheral leucocytes) was carried out on all women with PCOS as well as controls. Statistical Analysis: Student "t" test for quantitative and Chi-square test for nominal variables was used. For estimation of risk, odds ratio and 95% confidence interval were calculated. Results: The odds ratio of bearing a heterozygous genotype (CT) was 1.32 in women with PCOS as compared to controls (P = 0.48). No homozygous mutation (TT) was found in the study population. Serum cholesterol was more in heterozygous (CT) genotype (215.48 ± 25.56 mg/dl) as compared to normal (CC) genotype (203.29 ± 16.35 mg/dl) in women with PCOS ( P = 0.01). Similarly, serum triglyceride was more in heterozygous (CT) genotype (95.86 ± 37.34 mg/dl) as compared to normal (CC) genotype (82.36 ± 20.88 mg/dl) in women with PCOS ( P = 0.04). Conclusions: Although not statistically significant, there is a slightly higher prevalence of heterozygous (CT) genotype in women with PCOS. MTHFR C677T polymorphism when present may confer an increased susceptibility to develop hyperlipidemia in women with PCOS. More prospective studies are needed to confirm whether this hyperlipidemia due to MTHFR C677T polymorphism clinically manifests into CAD in long term in women with PCOS.


Keywords: CAD, coronary artery disease, hyperlipidemia, MTHFR C677T polymorphism, PCOS, polycystic ovary syndrome


How to cite this article:
Jain M, Pandey P, Tiwary NK, Jain S. MTHFR C677T polymorphism is associated with hyperlipidemia in women with polycystic ovary syndrome. J Hum Reprod Sci 2012;5:52-6

How to cite this URL:
Jain M, Pandey P, Tiwary NK, Jain S. MTHFR C677T polymorphism is associated with hyperlipidemia in women with polycystic ovary syndrome. J Hum Reprod Sci [serial online] 2012 [cited 2019 Nov 22];5:52-6. Available from: http://www.jhrsonline.org/text.asp?2012/5/1/52/97802



   Introduction Top


Polycystic ovary syndrome (PCOS) is considered to be the most common endocrine disorder affecting women. [1] It is the most common cause of anovulatory infertility and hirsutism. [2],[3] About 15% women of reproductive age group are affected. [4] Women with PCOS in long term are known to exhibit adverse cardiovascular risk profile - obesity, dyslipidemia, hypertension, insulin resistance and hyperinsulinemia [5] and an increased risk of premature coronary artery disease (CAD). [6]

Hyperhomocysteinemia is associated with hyperlipidemia [7] and is an independent risk factor for CAD. [8] Moreover, hyperhomocysteinemia has been positively associated with hyperinsulinemia and insulin resistance in a number of studies. [9-13] In general population, the most common cause of hyperhomocysteinemia is reduced activity of MTHFR, an enzyme involved in folate-dependent remethylation of homocysteine to methionine. [14] This may either be due to dietary deficiency of folate or genetic MTHFR deficiency. Importantly, MTHFR gene C677T polymorphism encodes a thermolabile variant of the enzyme characterized by cytosine to thymine transition at nucleotide 677, characterized by alanine to valine substitution at codon 222 and 30% reduction in enzyme activity in heterozygous and 70% in homozygous genotypes. [14] Furthermore, MTHFR deficiency and resulting hyperhomocysteinemia can lead to impaired DNA methylation, [15],[16],[17] accumulation of dUMP with excessive incorporation of uracil into DNA and activation of repair mechanisms resulting in increased risk of chromosomal breakage, [18],[19] decreased nitric oxide formation, [20],[21] increased reactive oxygen species formation [22],[23] and proinflammatory cytokine release. [24] Female reproductive functions, especially folliculogenesis and oogenesis are very sensitive to the above-mentioned changes. Experimental data are in favor that hyperhomocysteinemia can be involved in maturity of oocytes, [25] ovulation, [26] proliferation and differentiation of granulosa cell and steroidogenesis. [27] All the above facts point towards a possible correlation between MTHFR and PCOS.

A number of studies found a positive correlation between hyperhomocysteinemia and insulin resistance and/or hyperandrogenemia in women with PCOS [28],[29],[30],[31],[32],[33] while many other studies did not. [34],[35] Association between PCOS and MTHFR C677T polymorphism has been investigated in various population groups [36],[37],[38],[39] with both positive and negative results. Since no study has been done in the Indian population, we designed this study in an effort to investigate a possible correlation between PCOS, its clinical and biochemical parameters, and MTHFR C677T polymorphism.


   Materials and Methods Top


A case-control study was designed taking 92 young women aged 18 - 30 years with PCOS and 95 age-matched healthy controls.

Inclusion criteria for selection of cases and controls

The Rotterdam ESHRE/ASRM-Sponsored PCOS consensus criteria [40] was used to diagnose PCOS. Women with presence of any 2 of the following 3 features were diagnosed as having PCOS:

  1. Oligomenorrhoea (menstrual cycle ≥ 45 days or < 8 cycles per year) and/or amenorrhoea (> 3 months).
  2. Clinical hyperandrogenism {presence of acne, hirsutism (Ferriman Gallwey score ≥ 8 [41] ) or alopecia}.
  3. Polycystic ovaries on sonography (≥ 12 follicles in one or both ovaries, 2 - 9 mm in diameter and/or increased ovarian volume ≥ 10 ml).


Controls were defined as healthy age-matched women with regular cycles, absence of clinically apparent hyperandrogenism, obesity, any chronic illness and who were not on medication.

Exclusion criteria

All patients with diabetes mellitus, hypertension, hyperprolactinemia, thyroid disorder, Cushing's syndrome, acromegaly, premature ovarian failure, virilising adrenal or ovarian tumors, and oral contraceptive pill use within last 6 months were excluded from the study. None of the subjects were alcoholic or smoker.

An informed consent was taken from all subjects. Proper clinical examination including anthropometry was done.

Biochemical and hormone analysis

Blood samples were drawn on day 2 of normal menstrual cycle or progesterone-induced bleeding after an overnight fast. Plasma glucose was measured by glucose oxidase peroxidase method (Selectra XL analyzer, Vital Scientifics, Holland). Plasma insulin, LH, FSH, prolactin and total testosterone were measured by chemiluminescent enzyme immunoassay using commercially available kits (Immulite 1000 systems, Siemens). Serum cholesterol, triglyceride, LDL and HDL levels were measured using kits by ERBA diagnostic, Mannheim, Germany. TSH levels were measured using IRMA kit (BARC, Mumbai, India).

Insulin resistance was calculated using the homeostasis model assessment-insulin resistance index (HOMA-IR) according to the following formula: [42]

HOMA-IR = Fasting serum insulin (μU/ml) × Fasting plasma glucose (mg/dl) 405

Sonography

Pelvic sonography (Nemio 30, Toshiba, Japan) was carried out on day 2 of menstrual cycle in both cases and controls.

Genetic analysis

Blood samples were collected in tubes containing EDTA and stored at 4°C. Genomic DNA was extracted from peripheral leukocytes by salting out procedure. [43] C677T variant of MTHFR gene was amplified using a forward primer 5′AGGCTGTGCTGTGCTGTTG3′ and reverse primer 5′CGCTCTGCAAGTTCTGGA3′ by polymerase chain reaction (Bio-Rad laboratories Inc., Berkeley, California). The PCR conditions were 30 cycles of 1 min at 94°C, 1 min at 68°C, 1 min at 72°C. The 477bp fragment generated was restricted digested with Hinf1 (Fermentas Life Sciences, Burlington, Canada) at 37°C for 1 hour. Subsequently, separation using 2% agarose gel electrophoresis was done followed by visualization under UV illuminator after ethidium staining (Gel documentation System, Alphalmager, USA).

Genotypes were expressed as CC for homozygous wild, CT for heterozygous and TT for homozygous mutant genotype. In CC genotype, the 477 bp was digested into 425 and 52 bp. In CT genotype, the 425 bp was further digested into 260 and 165 bp, thus leading to 4 fragments (425, 260, 165, 52). In TT genotype, 3 fragments of 260, 165 and 52 bp were formed.

Statistical analysis

SPSS 16.0 for Windows was used for statistical analysis. All quantitative variables (Continuous, interval-scaled or ratio scaled) were expressed as mean ± standard deviation while for qualitative variables, a frequency along with their respective percentage was given. The distribution for each variable was tested for normality. The comparison of means was done by Student "t" test. For nominal (categorical) variables, Chi-square (χ2 ) test was used. For estimation of risk, Odds ratio (OR) and 95% confidence interval (CI) were calculated. A P-value less than 5% (P < 0.05) was considered statistically significant.


   Results Top


The demographic, anthropometric, biochemical and hormonal parameters of the study population (cases and controls) were compared [Table 1].
Table 1: Demographic, anthropometric, biochemical and hormonal parameters of the study population (PCOS cases and controls)

Click here to view


Genotype distribution and allele frequency of MTHFR C677T polymorphism were compared in cases and controls [Table 2]. CT genotype was 1.32 times more in women with PCOS as compared to controls (P = 0.48). No homozygous mutant (TT) genotype was found in the study population.
Table 2: Genotype distribution and allele frequency of MTHFR C677T polymorphism in study population (PCOS women and Controls) along with Odds ratio and 95% CI

Click here to view


In women with PCOS, the demographic, anthropometric, biochemical and hormonal parameters were compared in relation to the 2 genotypes (CC and CT) [Table 3]. Serum cholesterol was more in heterozygous (CT) genotype (215.48 ± 25.56 mg/dl) as compared to normal (CC) genotype (203.29 ± 16.35 mg/dl) in women with PCOS (P = 0.01). Similarly, serum triglyceride was more in heterozygous (CT) genotype (95.86 ± 37.34 mg/dl) as compared to normal (CC) genotype (82.36 ± 20.88 mg/dl) in women with PCOS (P = 0.04). Fasting insulin levels were also increased in CT genotype (20.33 ± 3.47 μU/ml) as compared to normal (CC) genotype (19.0 ± 2.24 μU/ml) but did not reach statistical significance (P = 0.05).
Table 3: Demographic, anthropometric, biochemical and hormonal of women with PCOS according to the genotypes CC and CT of MTHFR gene C677T polymorphism

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   Discussion Top


C677T polymorphism of MTHFR gene causes decreased activity of MTHFR enzyme [14] resulting in hyperhomocysteinemia, which is associated with hyperlipidemia. [7] As noted by Choi et al.,[38] development of therapeutic approaches is very necessary for women with PCOS, and the genetic association studies will provide insights into the role of MTHFR gene in the pathological milieu of PCOS. Present study shows a relative risk of 1.32 in Indian population for presence of CT genotype in women with PCOS (P = 0.33). Most studies done till date [36],[37],[38] did not find any significant correlation (P ≥ 0.05) between PCOS and MTHFR C677T polymorphism. Tsanadis et al. [36] found a relative risk of 1.2 (P = 0.83), while Karadeniz et al.[39] found a relative risk of 4.34 (P < 0.001). Although higher plasma homocysteine levels were found in women with PCOS (P < 0.05) as compared to controls, MTHFR C677T polymorphism was not found to influence these homocysteine levels (P = 0.19). [39] The differences in sample size as well as in difference in ethnicity between different population groups may explain the differences in result.

The results of our study show a novel relation between MTHFR C677T polymorphism and laboratory parameters of PCOS. CAD and type 2 DM being common in PCOS patients, the results of this study assumes importance. The finding of increased risk of MTHFR C677T polymorphism in PCOS together with the finding that heterozygous genotype (CT) is associated with hyperlipidemia signify that this can be a cause of women with PCOS developing CAD in later life. Simultaneous estimation of serum homocysteine and folate levels would have given better insight into the relation between dietary MTHFR deficiency, MTHFR C677T polymorphism, hyperhomocysteinemia, and PCOS. More studies need to be carried out in Indian and other population groups to see for correlation between MTHFR C677T polymorphism and PCOS and the clinical and biochemical findings of PCOS to further verify our results. Furthermore, long term prospective case-control studies taking larger population groups in different parts of the world would clarify whether the increased serum cholesterol and triglyceride levels manifest clinically into CAD in women with PCOS having this polymorphism, thus further clarifying the role of MTHFR gene. Taking plasma homocysteine and folate levels into consideration will give a better insight into pathogenesis of late sequelae of PCOS and its relation to MTHFR gene.


   Acknowledgement Top


We are thankful to the Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi for helping in genetic analysis of blood samples.

 
   References Top

1.Franks S. Polycystic ovary syndrome. N Engl J Med 1995;333:853-61.  Back to cited text no. 1
    
2.Adams J, Polson DW, Abdulwahid N, Morris DV, Franks S, Mason HD, et al. Multifollicular ovaries: Clinical and endocrine features and response to pulsatile gonadotrophin releasing hormone. Lancet 1985;1375-8.  Back to cited text no. 2
    
3.Hull MG. Epidemiology of infertility and polycystic ovarian disease: Endocrinological and demographic studies. Gynecol Endocrinol 1987;1:235-45.  Back to cited text no. 3
    
4.Legro RS. Polycystic ovary syndrome and cardiovascular disease: A premature association? Endocr Rev 2003;24:302-12.  Back to cited text no. 4
    
5.Glueck CJ, Papanna R, Wang P, Goldenberg N, Sieve-Smith L. Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome. Metabolism 2003;52:908-15.  Back to cited text no. 5
    
6.Talbott EO, Zborowskii JV, Boudraux MY. Do women with polycystic ovary Syndrome have an increased risk of cardiovascular disease? Review of the evidence. Minerva Ginecol 2004;56:27-39.  Back to cited text no. 6
    
7.Huang L, Song XM, Zhu WL, Li Y. Plasma Homocysteine and Gene Polymorphisms Associated with the Risk of Hyperlipidemia in Northern Chinese Subjects. Biomed Environ Sci 2008;21:514-20.  Back to cited text no. 7
    
8.Refsum H, Ueland PM, Nygard O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med 1998;49:31-62.  Back to cited text no. 8
    
9.Giltay EJ, Hoogeven EK, Elbers J, Gooren LJ, Asscheman H, Stehouwer CD. Insulin resistance is associated with elevated plasma total homocysteine levels in healthy, non-obese subjects [letter]. Atherosclerosis 1998;139:197-8.  Back to cited text no. 9
    
10.De Pergola G, Pannacciulli N, Zamboni M, Minenna A, Brocco G, Sciaraffia M. Homocysteine plasma levels are independently associated with insulin resistance in normal weight, overweight and obese pre-menopausal women. Diabetes Nutr Metab 2001;14:253-8.  Back to cited text no. 10
    
11.Ratnam S, Maclean KN, Jacobs RL, Brosnan ME, Kraus JP, Brosnan JT. Hormonal regulation of cystathionine-synthase expression in liver. J Biol Chem 2002;26:278-82.  Back to cited text no. 11
    
12.Sanchez-Margalet V, Valle M, Ruz FJ, Gascon F, Mateo J, Goberna R. Elevated plasma total homocysteine levels in hyperinsulinemic obese subjects. J Nutr Biochem 2002;13:75-9.  Back to cited text no. 12
    
13.Badawy A, State O, El Gawad SSh, El Aziz OA. Plasma homocysteine and polycystic ovary syndrome: The missed link. Eur J Obstet Gynecol Reprod Biol 2007;131:68-72.  Back to cited text no. 13
    
14.Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, et al. A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995;10:111-3.  Back to cited text no. 14
    
15.Stern LL, Mason JB, Selhub J, Choi SW. Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene. Cancer Epidemiol Biomarkers Prev 2000;9:849-53.  Back to cited text no. 15
    
16.Ueland PM, Hustad S, Schneede J, Refsum H, Vollset SE. Biological and clinical implications of the MTHFR C677T polymorphism. Trends Pharmacol Sci 2001;22:95-201.  Back to cited text no. 16
    
17.Friso S, Choi SW, Girelli D, Mason JB, Dolnikowski GG, Bagley PJ, et al. A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status. Proc Natl Acad Sci U S A 2002;99:5606-11.  Back to cited text no. 17
    
18.Blount BC, Mack MM, Wehr CM, MacGregor JT, Hiatt RA, Wang G, et al. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: Implications for cancer and neuronal damage. Proc Natl Acad Sci U S A 1997;94:3290-5.  Back to cited text no. 18
    
19.Fenech M. The role of folic acid and Vitamin B12 in genomic stability of human cells. Mutat Res 2001;475:57-67.  Back to cited text no. 19
    
20.Zhang X, Li H, Jin H, Ebin Z, Brodsky S, Goligorsky MS. Effects of homocysteine on endothelial nitric oxide production. Am J Physiol Renal Physiol 2000;279:F671-8.  Back to cited text no. 20
    
21.Romerio SC, Linder L, Nyfeler J, Wenk M, Litynsky P, Asmis R, et al. Acute hyperhomocysteinemia decreases NO bioavailability in healthy adults. Atherosclerosis 2004;176:337-44.  Back to cited text no. 21
    
22.Starkebaum G, Harlan JM. Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. J Clin Invest 1986;77:1370-6.  Back to cited text no. 22
    
23.Weiss N. Mechanisms of increased vascular oxidant stress in hyperhomocysteinemia and its impact on endothelial function. Curr Drug Metab 2005;6:27-36.  Back to cited text no. 23
    
24.Poddar R, Sivasubramanian N, DiBello PM, Robinson K, Jacobson D. Homocysteine induces expression and secretion of monocyte chemo attractant protein-1 and interleukin-8 in human aortic endothelial cells: Implications for vascular disease. Circulation 2001;103:2717-23.  Back to cited text no. 24
    
25.Szymanski W, Kazdepka-Zieminska A. Effect of homocysteine concentration in follicular fluid on a degree of oocyte maturity. Ginekol Pol 2003;74:1392-6.  Back to cited text no. 25
    
26.Willmott M, Bartosik DB, Romanoff EB. The effect of folic acid on superovulation in the immature rat. J Endocrinol 1968;41:439-45.  Back to cited text no. 26
    
27.Mohanty D, Das KC. Effect of folate deficiency on the reproductive organs of female rhesus monkeys: A cytomorphological and cytokinetic study. J Nutr 1982;112:1565-76.  Back to cited text no. 27
    
28.Yarali H, Yildirir A, Aybar F, Kabakci G, Bukulmez O, Akgul E, et al. Diastolic dysfunction and increased serum homocysteine concentrations may contribute to increased cardiovascular risk in patients with polycystic ovary syndrome. Fertil Steril 2001;76:511-6.  Back to cited text no. 28
    
29.Loverro G, Lorusso F, Mei L, Depalo R, Cormio G, Selvaggi L. The plasma homocysteine levels are increased in polycystic ovary syndrome. Gynecol Obstet Invest 2002;53:157-62.  Back to cited text no. 29
    
30.Schachter M, Raziel A, Friedler S, Strassburger D, Bern O, Ron-El R. Insulin resistance in patients with polycystic ovary syndrome is associated with elevated plasma homocysteine. Hum Reprod 2003;18:721-7.  Back to cited text no. 30
    
31.Vrbikova J, Tallova J, Bicikova M, Dvorakova K, Hill M, Starka L. Plasma thiols and androgen levels in polycystic ovary syndrome. Clin Chem Lab Med 2003;41:216-21.  Back to cited text no. 31
    
32.Bayraktar F, Dereli D, Ozgen AG, Yilmaz C. Plasma homocysteine levels in polycystic ovary syndrome and congenital adrenal hyperplasia. Endocr J 2004;51:601-8.  Back to cited text no. 32
    
33.Wijeyaratne CN, Nirantharakumar K, Balen AH, Barth JH, Sheriff R, Belchetz PE. Plasma homocysteine in polycystic ovary syndrome: Does it correlate with insulin resistance and ethnicity? Clin Endocrinol (Oxf) 2004;60:560-7.  Back to cited text no. 33
    
34.Kilic-Okman T, Guldiken S, Kucuk M. Relationship between homocysteine and insulin resistance in women with polycystic ovary syndrome. Endocr J 2004;51:505-8.  Back to cited text no. 34
    
35.Yilmaz M, Biri A, Bukan N, Karakoc A, Sancak B, Toruner F, et al. Levels of lipoprotein and homocysteine in non-obese and obese patients with polycystic ovary syndrome. Gynecol Endocrinol 2005;20:258-63.  Back to cited text no. 35
    
36.Tsanadis G, Vartholomatos G, Korkontzelos I, Avgoustatos F, Kakosimos G, Sotiriadis A, et al. Polycystic ovarian syndrome and thrombophilia. Hum Reprod 2002;17:314-9.  Back to cited text no. 36
    
37.Orio F Jr, Palomba S, Di Biase S, Colao A, Tauchmanova L, Savastano S, et al. Homocysteine levels and C677T polymorphism of methylenetetrahydrofolate reductase in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003;88:673-9.  Back to cited text no. 37
    
38.Choi SW, Gu BH, Ramakrishna S, Park JM, Baek KH. Association between a single nucleotide polymorphism in MTHFR gene and polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 2009;145:85-8.  Back to cited text no. 38
    
39.Karadeniz M, Erdogan M, Zengi A, Eroglu Z, Tamsel S, Olukman M, et al. Methylenetetrahydrofolate reductase C677T gene polymorphism in Turkish patients with polycystic ovary syndrome. Endocrine 2010;38:127-33.  Back to cited text no. 39
    
40.The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Working Group 2004. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19:41-7.  Back to cited text no. 40
    
41.Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol 1961;21:1440-7.  Back to cited text no. 41
    
42.Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-9.  Back to cited text no. 42
    
43.Miller SA, Dykes DD, Polesky HF. A simple salting-out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.  Back to cited text no. 43
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]


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