Gly15Gly polymorphism within the human adipocyte-specific apM-1gene but not Tyr111His polymorphism is associated with higher levels of cholesterol and LDL-cholesterol in caucasian patients with type 2 diabetes

Abstract

Frequency of apM-1 gene polymorphisms and their association with metabolic parameters was evaluated in a population-based sample of 556 type 2 (316 males / 240 females) diabetic patients. PCR-based RFLP analysis was performed in blood samples. The T --> G transition at nucleotide +45 within exon-2 [Gly15Gly] was detected with an allelic frequency of 0.91 for the wildtype allele and 0.09 for the mutated allele. The missense point mutation (TAC --> CAC) at nucleotide +331 within exon 3 [Tyr111His] was detected with an allelic frequency of 0.97 and 0.03, respectively. These frequencies did not differ from a non-diabetic cohort examined earlier. Concerning the Gly15Gly polymorphism, the TT-genotype was found in 457 (82.2%) and the TG-genotype in 99 (17.8%), concerning the Tyr111His polymorphism, TT-genotype was found in 525 (94.4) and TC-genotype in 31 (5.6%) of type 2 diabetic patients. In TG-genotype as compared to TT-genotype significantly more patients had LDL-serum levels in high LDL-classes (<150 mg/dl: 24.4% (TG) vs. 41.4% (TT), 150mg/dl to 190mg/dl: 40.0% (TG) vs. 33.9% (TT), >190 mg/l: 35.6% (TG) vs. 25.0% (TT); p = 0.010). No differences in serum levels of lipids were found in genotype-subgroups of the Tyr111His polymorphism. Thus, Gly15Gly polymorphism of apM-1 gene might play a role in dyslipidaemia in type 2 diabetic patients.

Kandidatengene des Diabetes mellitus Typ 2

“…Für die spezifische Amplifikation des Exons 2 und die anschließende RFLP-(Restriktionsfragmentlängenpolymor-phismen-)Analytik wurden die experimentellen Bedingungen einer früher publizierten Arbeit übernommen [8].…”

“…Hierfür wurden die Ergebnisse (2000)(2001)(2002)(2003)(2004) einer Auswahl von Polymorphismen in den Genen für PAI-1, PPARγ, UCP-1 und Adiponektin in einem populationsbezogenen Untersuchungskollektiv von Typ-2-Diabetikern in der Oberpfalz (Bayern) herangezogen und statistisch ausgewertet [7][8][9][10][11][12]. Als spezifisches Sekretionsprodukt (Adipokin) des weißen Fettgewebes wurde Adiponektin ausgewählt, als spezifisches Genprodukt des braunen Fettgewebes das UCP-1-Gen. PAI-1 wurde als ein mit Adipositas und Insulinresistenz assoziierter prothrombotischer Risikofaktor ausgewählt, welcher zudem in erheblichen Mengen vom viszeralen Fettgewebe gebildet wird.…”

Genetic effects of adiponectin on blood lipids and blood pressure

“…Three of the most commonly studied single nucleotide polymorphisms are a silent T to G substitution in exon 2 (+45 T > G, rs2241766), a G to T substitution in intron 2 (+276 G > T, rs1501299) and a C to G substitution in the immediate 5’ flanking region of the gene (−11377 C > G, rs266729) 1 . A number of investigators have studied the possible association of the three polymorphisms with blood lipids and blood pressure, but owing to differences in ethnic populations, environmental factors and study power, the results are conflicting and inconclusive 7–41 . In this study, a meta‐analysis was performed on previous reports to investigate the association of the ADIPOQ gene polymorphisms with blood lipids and blood pressure.…”

Interactions Between Noncontiguous Haplotypes in the Adiponectin Gene ACDC Are Associated With Plasma Adiponectin

“…Plates were read using an ABI 7900 machine with automatic allele calling, supplemented as necessary with manual allele calling, especially for SNPs of low minor allele frequency (Ͻ0.05). SNP ϩ45 was genotyped using a PCR-based restriction fragment-length polymorphism protocol described by Zeitz et al (31). Details about sample processing and genotyping protocols are included in Supplemental Table 1, which is detailed in the online appendix (available at http://diabetes.diabetesjournals.org).…”