| dc.description.abstract | Background: Calpain 10 (CAPN10) gene is involved in a wide variety of
cellular processes, among them the exocytosis of insulin. CAPN10 presents
polymorphic variants that have been associated with diabetes mellitus type 2
(DM2), particularly the SNP-43, SNP-19, and SNP-63, as well as haplotypes
formed by these polymorphisms.
Objective: To determine whether there is association between the
polymorphisms SNP-43, SNP-19, and SNP-63 of theCAPN10 gene and DM2
patients in Sinaloa.
Material and methods: We analyzed 200 patients with DM2 and 140
controls, both residents of Sinaloa. Simple PCR was applied for the
identification of alleles of SNP-19, and for the SNP-43 and SNP-63 real
timePCR was used. Several tests and software according to the data being
compared were used for statistical analysis (t of student, Chi-square, Fisher
Exact,Odds ratio, and the software Hapstat 3.0).
Results. In general, analyzed polymorphisms do not show significant
differences between cases and controls, and all themare in the Hardy-
Weinberg equilibrium. For SNP-43 controls allele frequencies were G=70%
and A=30%, for cases G=72% and A=28%. The genotype frequencies in
controls were 49%, 43% and 9% for GG, GA and AA, respectively; while in
the cases they were observed in 51%, 42%, and 7%, respectively. Regarding
to the SNP-19, the frequency of the allele 1 (del) was 32%, and the allele 2
(ins) 68% in controls; while in patients they were 39% and 61%, respectively.
The ins/ins genotype has a frequency of 36%in controls and 46% in cases;
the heterozygote ins/del a frequency of 51% in controls and 43% in cases
and the homozygous del/del controls 13% and 11% in cases. SNP-63, the
allele frequencies were C=87% and T=13% for controls, and C=83% and
T=77% for the cases. The genotype frequencies were 76% (CC), 23% (CT),
and 1% (TT), and 70%, 27%, and 3% for controls and patients, respectively.
Moreover, to comparing control women versus case women we found an
association of the allele 1 of theSNP-19to DM2 (OR=1.52, p=0.04).
Haplotype analysis showed a protective effect for combination 122 (OR=0.044; p=0.001).
Discussion: We found no significant differences to compare allele frequency
and genotype in our population for the polymorphism SNP-43, SNP-19, and
SNP-63, which is similar to that found in other populations. However, there
are also differences with other studies. For example, for the SNP-43, the G
allele and the GG genotype have been associated with increased risk for
DM2, low concentrations of glucose in plasma, reduction of mRNA
expression in skeletal muscle, high concentrations of insulin and fatty acid.
The SNP-19 1/1 genotype has been related with a decrease in lipolytic
activity, and genotype 2/2 to a high body mass index. In our study the allele 1
(del) was associated with DM2 only in women (OR=1.52, p=0.04). Regard to
SNP-63, association of the allele T and DM2 has been reported.
The haplotype 122 was only present in the group control (p=0.001), which
may suggest a protect effectversusDM2. This could be a fortuitous finding,
because it has not been reported as a haplotype of protection in other
studies. The haplotype 222 was associated with DM2, but there were no
significant differences (p=0.14). In this sense the haplotype 111 has been
associated with risk for DM2 in Arabs (p=0.034).
Conclusion: Even if a bias could be in the interpretation of our observations
because of the size analyzed sample, we must not discard alleles or
haplotypes of DM2 risk in our population. | |
