Non-Association of Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms with Homocysteine Levels, Venous or Arterial Thromboses in 1,141 North-Central Appalachian Patients

Farhad Khimani,Peter Perrotta,Gerry Hobbs,Thomas Hogan

doi:10.5539/cco.v5n2p21

Farhad Khimani, Peter Perrotta + Show 2 more

Open Access

https://doi.org/10.5539/cco.v5n2p21

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Abstract

Objectives: MTHFR polymorphism testing has been used by clinicians for thrombophilia risk assessment. We questioned the utility of such testing.Methods: 1,141 patients age 18 and above had MTHFR testing for both C677T and A1298C polymorphisms, 2006 through 2012. Available plasma homocysteine levels were obtained and ICD-9 billing codes were grouped to identify venous or arterial clots in these patients.Results: 901 women and 240 men were tested; median age in women was 33 years (range 18-86); median age in men was 47 years (range 18-83). County of residence mapping confirmed that this MTHFR tested population was from north-central Appalachia. Only 144 (13%) of the 1,141 patients had no polymorphism at either the C677T or the A1298C locus; only 4 patients (0.4%) had 3 or more polymorphisms; 993 patients (87%) had either one or two polymorphisms. We found polymorphism frequency pattern similar in both sexes. Although men had higher homocysteine levels, MTHFR polymorphisms did not associate with homocysteine levels in either sex. In 901 women tested, the ICD-9 coded incidence of arterial clots was 20%, and of venous clots was 21%; in 240 men tested, the incidence of arterial clots was 48% and of venous clots was 40%. MTHFR polymorphisms did not associate with arterial or venous clots in either sex. Based on CPT billing codes, a minimal cost estimate was $137,000 for performing these 1,141 MTHFR tests.Conclusions: MTHFR testing was costly and did not add useful information during thrombophilia evaluation in this patient population.

Highlights

Associating MTHFR polymorphisms with thrombosis or embolism has been controversial, and there is a growing consensus that MTHFR genetic testing should not be done for thrombophilia evaluation [USPSTF 2009, Leewood 2012; Hickey et al, 2013].http://cco.ccsenet.orgCancer and Clinical OncologyVol 5, No 2; 2016When we noted that ~90% of patients referred to our benign hematology clinic at West Virginia University Hospital (WVUH) had MTHFR polymorphisms [Gadiyaram et al, 2009], we decided to study all patients tested for both MTHFR C677T and A1298C polymorphisms at WVUH from 2006 through 2012, comparing the test results with homocysteine levels and ICD-9 codes identifying venous or arterial clots in the same tested patients
Men had higher homocysteine levels, MTHFR polymorphisms did not associate with homocysteine levels in either sex
Plasma homocysteine levels were tested and available in 610 patients and these levels were compared to MTHFR polymorphisms

Summary

Introduction

Associating MTHFR polymorphisms with thrombosis or embolism has been controversial, and there is a growing consensus that MTHFR genetic testing should not be done for thrombophilia evaluation [USPSTF 2009, Leewood 2012; Hickey et al, 2013].http://cco.ccsenet.orgCancer and Clinical OncologyVol 5, No 2; 2016When we noted that ~90% of patients referred to our benign hematology clinic at West Virginia University Hospital (WVUH) had MTHFR polymorphisms [Gadiyaram et al, 2009], we decided to study all patients tested for both MTHFR C677T and A1298C polymorphisms at WVUH from 2006 through 2012, comparing the test results with homocysteine levels and ICD-9 codes identifying venous or arterial clots in the same tested patients.

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