A high incidence of patients with MTHFR (methylenetetrahydrofolate reductase) gene mutations noted in an Appalachian population seen for thrombophilia at the West Virginia University hospitals, 2006-2012

Details

• Personal Author:
  Hobbs GR ; Hogan TF ; Khimani F ; Perrotta PL
• Description:
  Background We noted a higher than expected incidence of MTHFR gene mutations C677T or A1298C in Appalachian patients; a review of 72 patients was presented at American Society of Hematology meeting in 2009. To further evaluate the finding, we looked at 1378 patients, seen at our hospital for thrombophilia work up from 2006-2012 and this is an update to our previous report. Studies have suggested an increased risk of thromboembolism in patients with hyperhomocysteinemia. C677T mutation in the MTHFR gene has been thought responsible for hyperhomocysteinemia. However, the association of MTHFR gene mutations C677T and A1298C and thromboembolism, remains controversial. Methods We reviewed records of 1378 patients for risk factors for acquired or inherited thrombophilia. These patients include both inpatients and outpatients, seen at our institution from 2006-2012 for thrombophilia evaluation and had MTHFR testing done. All available risk factors and laboratory results were reviewed. Results 1378 patients had testing done for MTHFR from 2006-2012. Of 1378 patients 1072(77.7%) were females and 306(22.2%) were males. Median age was 35 years (range18-86). 1161 of the 1378(84%) patients had one or more positive mutations, with alleles C677TT (11.3%-high risk), C677T (25.7%), A1298CC (9%) and A1298C (20.5%). Further 268(19.4%) patients were compound heterozygote and had C677T-A1298C high risk mutation. Thus, 30.7% of all patients tested had a "high risk: MTHFR gene mutation. Coagulation profile of 1378 patients is depicted in Figure 1. Conclusion: Inherited risk factors in patients with established thromboembolism in our patient population is tabulated above. The factor II and factor V mutation incidences of 4.7% and 8.2%, as well the number of abnormalities in Protein C, protein S and anticardiolipin antibody appear similar to data reported in the literature for Caucasian populations. However, Rodrigues et al reported C677TT and C677T prevalence of 14-19% and 36-47% respectively in 1277 normal persons and A1298CC and A1298 C prevalence of 7-11% and 28-35% respectively(Am J Clin Nutr 2006;83:701). In our Appalachian population, the overall incidence of MTHFR mutations previously reported by our group in a small sample size (72) to be 88% still stands true in a larger sample size(1378) per our report but the distribution of the high risk mutations probably is not as high as reported earlier by our group. The incidence of MTHFR high risk mutation in Appalachian population is in accordance with previous population based studies. [Description provided by NIOSH]
• Subjects:
  Aging Antibodies Laboratories Men Mutagens Occupational Health Risk Assessment Risk Factors Safety Women
• Keywords:
  Age Groups Humans Laboratory Testing Proteins Risk Factors Statistical Analysis
• ISSN:
  0361-8609
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  89
• Issue:
  6
• NIOSHTIC Number:
  nn:20049504
• Citation:
  Am J Hematol 2014 Jun; 89(6):E57
• Federal Fiscal Year:
  2014
• Performing Organization:
  West Virginia University
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  American Journal of Hematology
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:501e80fb933857dbeac4301378877009fcff87ad72e4d84d234cef6c9a1749cf6b1442e1b24a8cd429773a0412177eb1f515d1a8f1924bfb0890e3d79f19fd83
• Download URL:
  https://stacks.cdc.gov/view/cdc/203944/cdc_203944_DS1.pdf
• File Type:
  [PDF - 581.16 KB ]