Association study of the Vitamin D: 1alpha-hydroxylase (CYP1alpha) gene and type 2 diabetes mellitus in a Polish population

• Published in: Diabetes & metabolism 2003-04, Vol.29 (2), p.119-124
• Main Authors: Malecki, MT, Klupa, T, Wolkow, P, Bochenski, J, Wanic, K, Sieradzki, J
• Format: Article
• Language: English
• Subjects: Cytosine; Diabetes Mellitus - enzymology; Diabetes Mellitus - genetics; Diabetes Mellitus, Type 2 - enzymology; Diabetes Mellitus, Type 2 - genetics; Diabète de type 2; Gene; Genetic Markers; Genotype; Gène; Humans; Introns; Obesity; Poland; Polymorphism; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Polymorphisme; Reference Values; Steroid Hydroxylases - genetics; Thymine; Type 2 Diabetes; Vitamin D 1Alpha-Hydroxylase; Vitamine D 1alpha-hydroxylase
• ISSN: 1262-3636; 1878-1780
• DOI: 10.1016/S1262-3636(07)70017-4

Type 2 diabetes mellitus (T2DM) is a complex disease. Genetic and environmental factors cooperate together to form its clinical picture. Polymorphisms in genes involved in the metabolism of vitamin D may influence susceptibility to T2DM. One of them is the vitamin D 1alpha-hydroxylase (CYP1alpha) gene. In this study we searched for the association of two markers, one in its intron 6 and the another one located upstream from the 5′ end of CYP1alpha gene, with T2DM in a Polish population. Overall 522 individuals were included in this study: 291 T2DM patients and 231 controls. The sequences, which contain both examined variants, were amplified by polymerase chain reaction (PCR). The T→C polymorphism in intron 6 was assessed by the dot-blotting method using P 32. Genotyping of the other variant in the 5′ end of CYP1alpha gene was carried out by restriction fragment length polymorphism (RFLP) method. Since variants of both SNPs were in very strong linkage disequilibrium, haplotypes could be assigned to phase-unknown individuals. The distribution of alleles, genotypes, haplotypes and haplotype combinations was compared between the groups by χ 2 test. The frequency of T/C alleles of the 5′end variant was 81.7%/18.3% in T2DM patients and 82.8%/17.2% in the controls (χ 2 = 0.2, 1.d.f., p = 0.65). For a T→C polymorphism in intron 6 the frequency of alleles was 65.1%/34.9% and 67.5%/32.5% in T2DM patients and controls, respectively (χ 2 = 0.413, 1.d.f., p = 0.669). Distribution of genotypes, haplotypes and haplotype combinations were similar in both groups. In stratified analysis, we observed that the T-C/T-T heterozygous haplotype combination was more prevalent in the subgroup of obese T2DM patients (BMI ≥ 30) than in the controls (41.5% vs 28.6%, p = 0.01). Vitamin D 1alpha-hydroxylase is not a major gene for T2DM in a Polish population. However, this gene may be associated with T2DM in subjects with obesity. Thus, to definitely determine the role of this gene in T2DM further studies are necessary in other populations using larger sample size. Liens entre le gène de la vitamine D: 1alpha-hydroxylase (CYP1alpha) et le diabète de type 2 dans une population polonaise Le diabète de type 2 (T2DM) est un maladie complexe, dont la présentation clinique résulte de la coopération entre des facteurs génétiques et environnementaux. Des polymorphismes de gènes impliqués dans le métabolisme de la vitamine D pourraient influencer la susceptibilité au T2DM. L'un de ces gènes est