Transcript HFE MUTATIONS IN OCEANIAN PEOPLE (MELANESIAN AND

HFE MUTATIONS IN OCEANIAN PEOPLE (MELANESIAN AND POLYNESIAN)
G. Dine 1,2, G. Fumagalli 2, L.A Marquet 1, F. Van Lierde 2, V. Genty 2, R. Donnadieu 3, Y. Barguil 4,, S. Mermond 5, O. Hermine 1,6, J.F Toussaint 1,7
1-IRMES, Paris − 2-IBT, Troyes − 3-Direction Jeunesse et Sports de Nouvelle−Calédonie, Nouméa − 4-Hôpital Gaston Bourret, Nouméa − 5-Institut Pasteur de Nouvelle−Calédonie, Nouméa −
6-Hôpital Necker, Paris − 7-AP−HP, Hôtel−Dieu, Paris
Introduction
Results
Homozygous mutations of the HFE gene lead to hemochromatosis. In
Europe, it is mainly associated with the C282Y mutation. Other mutations
are involved in the disturbance of the iron metabolism, particularly H63D.
Previous international studies reveal significant frequency, notably for the
H63D mutation, among European populations.
Methods
No C282Y mutation has been found. However, at the heterozygotic
state, three H63D mutations have been identified in the Melanesian
group (2 women and 1 man) and four in the Polynesian group (1
woman and 3 men). There is no significant difference between both
groups. The frequency in the general Oceanian population is 7/119
and more precisely 3/66 in the Melanasian group and 4/53 in the
Polynesian group. Concerning the biological datas, hemoglobin levels
of mutated male subjects appear slightly higher than the levels of non
mutated male participants (p=0,09). Non mutated subjects have lower
Stfr level than the mutated subjects (p=0.03). The mutated subjects
don’t have any difference with the non mutated participants for the
glycated hemoglobin.
We carried out a preliminary study in 2011 aiming at measuring the HFE
mutations frequency among an Oceanian population from South Pacific in
New−Caledonia. Each volunteer provided a full written consent, approved
by the Necker Hospital Ethic Committee. The blood tests were done at the
elbow fold. The following biological analyses were completed on the blood
samples: complete blood count, serum iron, transferrin saturation, ferritin,
glycated hemoglobin. Among the collected blood samples, 2 EDTA tubes
per subject were repatriated for DNA extraction and gene assays in the IBT
laboratory.
The study included 119 subjects (66 Melanesian and 53 Polynesian), range
13−35 years (mean age 23±4.47). The participants were considered of
Melanesian or Polynesian origin on the basis of two−generation
autochthonous ancestry. Subjects born from miscegenation were excluded,
in particularly European. The repartition gave a male/female ratio of 0.78
for Melanesian subjects (29 men and 37 women) and of 1.4 for Polynesian
subjects (31 men and 22 women).
The genetic assays done with the Vienna Lab method covered the
following mutations: HFE mutations (V53M, V59M, H63D, H63H, S65C,
Q127H, P160delC, E168Q, E168X, W169X, C282Y, Q283P), TFR2 gene
(E60X, M172K, Y250X, AVAQ594−597del) and FPN1 gene (N144H,
V162del).
To assess the different biological parameters between mutated and non
mutated subjects, we conducted t−tests.
In « BioIron 2013 » Ed. International BioIron Society, 2013, 276 (abstract)
Discussion
This preliminary work has been done among an Oceanian
population in differentiating Melanesian from Polynesian origin. The
C282Y, the HFE allele most commonly associated with the hereditary
hemochromatosis among persons of European descent, has not been
identified in the Oceanian population. But we highlight the H63D at
the heterozygotic state without any deleterious consequence on the
iron metabolism or the glycemic regulation.
Conclusion
This work is the first to inform about the situation in the native
population of Pacific. This study suggests the presence of the H63D
mutation in subjects with a lower frequency than in the already
studied European populations.