European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Genetic analysis, linkage, and association
of IL-1α(Τ/C), IL-1β(-511)(T/T) and TGF-β(cd10/25) (CG/TG) was
observed when comparing the osteonecrosis group with the control
group (pT polymorphism and osteoporotic
phenotypes in Spanish postmenopausal women
L. Agueda 1,2 , M. Bustamante 1,2 , S. Jurado 3 , X. Nogués 3 , L. Mellibovski 3 , A.
Díez-Pérez 3 , S. Balcells 1,2 , D. Grinberg 1,2 ;
1 Dept. Genetics University of Barcelona, Barcelona, Spain, 2 CIBERER, ISCIII,
IBUB, Barcelona, Spain, 3 URFOA-IMIM Hospital del Mar, Barcelona, Spain.
Osteoporosis is a multifactorial disease, with a genetic component.
Several candidate genes have been proposed, among them MTHFR
(encoding methylenetetrahydrofolate reductase). This gene, associated
with several diseases, has been hypothesised to play a role in
osteoporosis through interference of collagen maturation caused by
elevated homocysteine. Additionally, a QTL for bone mineral density
(BMD) was mapped to Chr1, where MTHFR is located. In particular,
the c.677C>T polymorphism of this gene, is responsible for increased
homocysteine plasma levels. Recently, an association of this polymorphism
with lower BMD and increased risk of fractures has been described
in several populations. Our aim was to replicate these findings
in a Spanish postmenopausal cohort, performing association analyses
with femoral neck (FN), lumbar spine (LS) BMD and osteoporotic
fracture. Genotyping was performed by PCR-RFLP in 950 postmenopausal
women (mean age 55.6 ± 8.7). The association analysis was
performed by lineal regression for BMD and by logistic regression
for fracture. The minor allele frequency in our population was 39.7%
and the distribution of genotypes was in Hardy-Weinberg equilibrium
(p=0.521). No association was observed between the polymorphism
and either LS BMD (n=944, p=0.26 recessive model), or FN BMD
(n=564, p= 0.49 recessive model). For the presence of osteoporotic
fracture, the results were also negative (n=835, p=0.20). In conclusion,
this polymorphism is not associated with these osteoporotic phenotypes
in our cohort.
P1058. Vitamin D receptor and osteocalcine HindIII gene
polymorphism and bone mineral parameters in people, who
lived in Blockaded Leningrad during 1941-1944.
M. M. Kostik 1 , M. A. Bogdanova 1 , A. N. Voitovich 1 , O. S. Romashkina 1 , S. I.
Yagashkina 2,3 , O. N. Semenova 2 , V. I. Larionova 1 ;
1 State Pediatric Medical Academy, Saint-Petersburg, Russian Federation,
2 Researche Center for People, who lived in Blockaded Leningrad, Saint-Petersburg,
Russian Federation, 3 Military Medical Academy, Saint-Petersburg,
Russian Federation.
Osteoporosis is well-known phenomena in old population. Starvation
of Leningrad children during blockade 1941-1944 resulted in total dystrophy.
Hungry children weren’t accumulate peak bone mass and they
have high risk of osteoporosis realisation.
The mean age of 48 patients, included in our study was 8,64±5,12
years in 1941 was. Bone mineral parameters were detected by DEXA.
ApaI, TagI vitamin D receptor (VDR) and Hind III osteocalcine genes
polymorphism were detected by PCR.
Femur neck osteopenia people were elder in the end of blockade,
when people without OP (p=0,006). We have revealed differences in
TagI genotypes distribution between people with and without osteopenia
(OP) Wards zone (p=0,04), trochanter (p=0,05), L 1 -L 4 (p=0,01), and
differences in ApaI genotypes distribution between males (p=0,05), all
patients (p=0,03) with and without OP L 1 -L 4 . Males with t allele had significant
higher BMC femur neck, BMC, BMD, T score Wards zone, BMD
trochanter, females had higher T score Wards zone, BMC, T score trochanter,
BMC, BMD L 1 -L 4. Females with A allele had higher BMC, BMD
L 1 -L 4.
Females with and without OP L 1 -L 4 had differences in HindIII genotype
(p=0,05) and alleles distribution (p=0,049). People with and without
OP proximal part of femur had differences in genotype (p=0,03) distribution.
Females with H allele had significant higher BMC, BMD, Tscore
of femur neck, Wards zone, proximal part of femur (total), L 1 -L 4 .
Conclusion: TT genotype and T allele of TagI, aa genotype ApaI VDR
and h allele of HindIII osteocalcine gene polymorphism associated
with osteoporosis in people, who lived in Blockaded Leningrad during
1941-1944.
P1059. Research of MspI(a) and PvuII(a) polymorphism of PAH
gene in Kazakhstan
G. S. Svyatova 1 , M. G. Orazgalieva 1 , V. L. Akhmetova 2 ;
1 THE REPUBLICAN SCIENTIFIC RESEARCH CENTRE OF MOTHER AND
CHILD HEALTH PROTECTION, Almaty, Kazakhstan, 2 Institute of biochemistry
and genetics, Ufa, Russian Federation.
We investigated the frequencies distribution of polymorphic MspI(a) locus
in 8 intron and PvuII(a) locus in 2 intron of PAH gene. For research
we have taken DNA from blood of 100 not related representatives of
the Kazakh nation. In the Kazakh population the most often genotypes
were a MspI(à)*À/*à (0,58) and PvuII(a)*À1/*À2 (0,57). There were
no deviation in distribution of frequencies of a MspI(à) and PvuII(a)genotypes
from Hardy-Weinberg equilibrium. In the Kazakh populations
allele MspI(à)*À (frequency 0,57) and PvuII(a)*À2 (0,59) were
most often.
We have done the comparative analysis of distribution of frequencies
MspI(a) and PvuII(a) alleles of a gene PAH. We have found out distinctions
in the MspI(a) alleles between sample of the Kazakhs and
Russian (χ 2 =5,122, ð=0,034), French (χ 2 =5,785, ð=0,024), Udmurts,
Mordvins, Maris(χ 2 =5,122, ð=0,032) and Chinese (χ 2 = 27,955, ð<
0,001) [Daiger et al., 1989; Akhmetova V., 2001]. Observed heterozygosity
was 0,57. This meaning was higher than in populations of
Volga-Ural region of Russia (0,50). In the PvuII(a) alleles we have
found out distinctions between sample of the Kazakhs and populations
of Germany (χ 2 =7,445, ð=0,01), Bulgaria(χ 2 =25,293, ð