ISSN 1022-7954, Russian Journal of Genetics, 2006, Vol. 42, No. 3, pp. 333–338. © Pleiades Publishing, Inc., 2006.
Original Russian Text © R.I. Khusainova, N.N. Khusnutdinova, E.K. Khusnutdinova, 2006, published in Genetika, 2006, Vol. 42, No. 3, pp. 421–426.
Hemochromatosis is a hereditary disease of iron
metabolism disturbance. It is characterized by progres-
sive accumulation of iron in various tissues, which leads to
defective functioning of many organs. Clinical symptoms
develop gradually to the age of 30 to 40 years, they are not
speciﬁc, and may be diagnosed as liver cirrhosis, diabe-
tes mellitus, cardiomyopathy, arthrosis, etc. [1, 2].
Hemochromatosis is one of the rare hereditary disor-
ders, which can be effectively and simply treated, if
diagnosed timely, before the development of cirrhosis
or diabetes mellitus [3, 4].
In European populations, the disease prevalence is one
in 300 to 500 individuals, while the carrier state is esti-
mated to be one in ten individuals (up to 10%) [5–8].
Hemochromatosis is genetically heterogeneous.
Several disease forms were described, which were
associated with different genes and characterized by
different mode of inheritance. The main form, type 1, is
caused by the
gene defects [9, 10]. The
uct is the transmembrane glycoprotein HFE, which acts
as a modulator (regulator) of iron absorption [11–13].
Type 2 is a juvenile hemochromatosis, associated with
gene (coding for hepcidin) . Type 3 is
caused by the mutations in the
gene (coding for
transferrin receptor) [15, 16]; type 4 is associated with
gene, encoding the intestine iron exporter,
ferroportin 1 , and type 5 is caused by the mutation
in the gene coding for ferritin subunit H . Types 1
to 3 are autosomal recessive, while types 5 and 6 are
autosomal dominant disorders.
gene studies are focused on two missence
, undoubtedly associated
with the disease . Identiﬁcation of the hemochro-
matosis-causing genetic defect will provide early diag-
nostics, population screening for the carrier state, as
well as the performance of medical genetic counseling.
Early disease diagnostics and treatment, in turn, pre-
vents tissue damage and decreases mortality rate
among the patients. The prevalence of the
tions in the world populations, as well as the disease
screening algorithm remain uncertain.
With the aim of identiﬁcation of heterozygous carri-
ers and establishment of the disease screening pattern,
as well as for the description of the gene pool ethnic
mutations in the
gene were examined in indigenous populations of Cen-
MATERIALS AND METHODS
DNA samples were obtained from healthy unrelated
individuals representing indigenous populations of
Central Asia, which linguistically belonged to the
Turkic branch of the Altaic linguistic family. These
were Kazakhs (258 individuals from Zhambyl’sk raion
of Almaty oblast, Zhalagashsk raion of Kyzylorda
oblast, and Abaisk raion of Kazakhstan), Uighurs (116
individuals from Almaty oblast of Kazakhstan), Uzbeks
(81 individuals, dispersed sample from Uzbekistan),
Kyrgyzes (31 individuals from Fergana oblast of
Uzbekistan), Turkmens (18 individuals from the Kar-
akalpakstan Republic, Uzbekistan), as well as Tajiks
(42 individuals from Samarkand oblast of Uzbekistan)
and Kurds (49 individuals, dispersed sample from
Kazakhstan), belonging to the Iranian group of Indo-
European linguistic family. Blood samples were col-
lected during expeditions conducted in 2001 through
2002, and were also provided by the Republican Center
for Mother and Child Health Protection, Kazakhstan
Ministry of Health, Almaty.
Analysis of the Hemochromatosis Gene (
, in the Populations of Central Asia
R. I. Khusainova, N. N. Khusnutdinova, and E. K. Khusnutdinova
Institute of Biochemistry and Genetics, Russian Academy of Sciences, Ufa Research Center, Russian Academy of Sciences,
Ufa, 450054 Bashkortostan, Russia; fax: (3472)35-60-88; e-mail: firstname.lastname@example.org
Received August 9, 2005
—Analysis of the
mutations in the
gene was carried out in 594 individuals
representing seven indigenous populations of Central Asia. Among the populations examined, mutation
was found in Uighurs with the frequency of 0.009, and in Kazakhs and Tajiks with the frequency of 0.012. The
mutation was absent in Uzbeks, Kyrgyzes, Kurds, and Turkmens. Mutation
was detected in all popula-
tions studied with the frequencies ranging from 0.024 (Tajiks) to 0.139 (Turkmens). Judging by the frequencies
of the mutations of interest, the populations examined occupied the intermediate position between the European
and Eastern Asian populations, which corresponded to their geographical position.