Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


DO Carriers of A MEFV Mutation Have Any Selective Advantage to A Pathogen Endemic In the Same Geography?

Ugurlu1,  Serdal, Engin2,  Aynur, Hatemi1,  Gulen, Ozgon3,  Gulay, Akyayla3,  Elif, Bakir2,  Mehmet, Ozdogan1,  Huri

MD, Division of Rheumatology, Department of Medicine, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey
MD, Department of of Infectious Diseases, Medical Faculty, University of Cumhuriyet, Sivas, Turkey
Nesiller Genetic Lab, Istanbul, Turkey

Background/Purpose:

To explain the high level of MEFV heterozygots in Mediterranean basin, it has been speculated that carriers of FMF mutations might have a selective advantage because of increased resistance to a pathogen endemic to this area. The carrier rate for MEFV gene in Sivas, a city in central Turkey is as high as 1:3. Crimean-Congo Hemorrhagic fever (CCHF) a tick-borne disease caused by an arbovirus, associated with high mortality, is also endemic in the same geographical region. This gave us a unique opportunity to test whether MEFV heterozygotes have any survival advantage in this ongoing CCHF endemic.

Methods:

MEFV gene mutations were detected with PCR analysis and direct sequencing of Exon 10 and Exon 2, in 100 patients with a definite diagnosis of CCHF followed in Cumhuriyet University, Sivas / Turkey, (mean age 45.6±17, 58 M: 42 F). All CCHF patients were classified into two groups in terms of disease severity (severe and mild), according to the predictive factors for fatal outcome reported by Swanepoel et al (1). MEFV gene mutations were also analyzed with the same methods in 91 healthy blood donors (HC) living in Sivas.

Results:

Among the 100 patients with CCHF, 65 had mild and 35 had severe disease. There were 11 deaths in the severe group. Among the CCHF patients 62 patients carried either an exon 10 or exon 2 mutation compared to 33 in the HC (p<0.001). This significant difference was due to the increase in Exon 10 mutations (41/100 vs 10/91, p<0.001) which disappeared when only Exon 2 mutations were considered (38/100 vs 26/91, p>0.1). The number of patients with 2 mutations were also significantly more common among CCHF group (p<0.001). Regarding exon 2 we determined a haplotype of 4 SNPs (at positions: 102, 138, 165, 202 ) in 32 patients compared to 9 in HC (p<0.001), and described 4 new mutations in Exon 10. In the mild group there were 37 and in the severe group 25 carriers (p>0.1). 63% of the survivors compared to 54% of those who died carried a MEFV mutation (p>0.1). The distribution of mutations with regard to disease severity did not reveal a significant difference. Also there was no difference between the number of mutations among survivors versus non-survivors.

Conclusion:

Carrying a MEFV gene Exon 10, but not Exon 2 mutation does seem to increase the risk of developing CCHF infection however does not influence disease severity and outcome.

References:

1)Swanepoel, R, Gill, DE, Shepherd, AJ, Leman, PA, Mynhardt, JH & Harvey, S. The clinical pathology of Crimean-Congo hemorrhagic fever.Rev Infect Dis. 1989 May-Jun;11 Suppl 4:S794–800

To cite this abstract, please use the following information:
Ugurlu, Serdal, Engin, Aynur, Hatemi, Gulen, Ozgon, Gulay, Akyayla, Elif, Bakir, Mehmet, et al; DO Carriers of A MEFV Mutation Have Any Selective Advantage to A Pathogen Endemic In the Same Geography? [abstract]. Arthritis Rheum 2011;63 Suppl 10 :168
DOI:

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