Calpain10 gene polymorphisms are associated with posttransplantation diabetes mellitus in Chinese renal allograft recipients

Abstract

Abstract: AIM: To investigate the association between the Calpain10 gene polymorphism and the risk of PTDM in Chinese renal allograft recipients.METHODS: Three single nucleotide polymorphisms (CAPN10 gene SNP-19,SNP-43,SNP-63) were genotyped in the cohort, which consisted of 97 renal allograft recipients with PTDM (PTDM group) and 301 renal allograft recipients without PTDM (control group).The genotypes of polymorphisms were performed by allele specific polymerase chain reaction (ASPCR), PCR-restriction fragment length polymorphism (PCR-RFLP). Logistic regression test was used to identify risk factors for PTDM development and calculate the odds ratio.RESULTS: The 11 and 12 genotypes of SNP-19 and the GG genotypes of SNP-43 were more common in patients with PTDM than those without PTDM (P<0.05). After adjustments for age, sex, body weight and BMI, the effect of genotype remained significant (11 vs 22, OR=1.502, 95%CI: 1.016-2.347, P=0.048; 12 vs 22, OR=1.764, 95%CI: 1.055-2.947, P=0.030) in SNP-19 and the patients carrying genotype GG had higher risk comparison with carriers with genotype AA or GA(OR＝2.190, 95%CI: 1.047-3.473, P=0.044)in SNP-43. But SNP-63 was not association with PTDM.CONCLUSION: The 1-allele in SNP-19 and GG genotype in SNP-43 of CAPN10 gene are the independent risk factors of PTDM in Chinese renal allograft recipients.

Key words: Renal allograft recipients, Posttransplantation diabetes mellitus, Risk factor, Calpain10 gene, Single nucleotide polymorphism (SNP)

CLC Number:

R968

YU Ai-rong, FAN Xing, LIU Hui-ming, XIN Hua-wen. Calpain10 gene polymorphisms are associated with posttransplantation diabetes mellitus in Chinese renal allograft recipients[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(8): 901-905.

References

[1] 余爱荣,范星,辛华雯,等. 肾移植术后糖尿病发病率与危险因素[J]. 药物流行病学杂志,2011,20(4): 169-172.
[2] 朱琳,曾昭全,魏文树,等.我院1例肾移植术后肺部感染患者的药学监护[J].中国临床药理学与治疗学,2011,16(11):1244-1247.
[3] Yu AR, Xin HW, Wu XC, et al. Adiponectin gene polymorphisms are associated with posttransplantation diabetes mellitus in Chinese renal allograft recipients[J]. Transplant Proc,2011,43(5):1607-1611.
[4] Permutt MA,Bernal ME,Inoue H. Calpain 10:the first positional cloning of a gene for type 2 diabetes[J]. J Clin Invest,2000,106(7):819-821.
[5] Cox NJ, Hayes MG, Roe CA,et al. Linkage of Calpain 10 to type 2 diabetes:the biological rationale [J].Diabetes,2004, 53(Suppl 1):19-25.
[6] Weedon MN, Schwarz PE, Horikawa Y, et al. Meta-analysis and a large association study confirm a role for calpain-10 variation in type 2 diabetes susceptibility[J]. Am J Hum Genet, 2003, 73(5): 1208-1212.
[7] 纪立农,陈陵霞,韩学尧,等. Calpain 10 基因多态性与中国人2型糖尿病遗传易感性的相关性研究[J].中国糖尿病杂志,2002,10(1):7-10.
[8] Chen SF, Lu XF, Yan WL. Variations in the calpain-10 gene are associated with the risk of type 2 diabetes and hypertension in northern Han Chinese population[J]. Chin Med J, 2007, 120(24):2218-2223.
[9] 李金娥,刘德敏,张喆. 钙蛋白酶10基因多态性与2型糖尿病胰岛素抵抗的研究[J].天津医药,2008,36(2):96-98.
[10] Kurzawski M, Dziewanowski K, Kedzierska K,et al. Association of calpain-10 gene polymorphism and posttransplant diabetes mellitus in kidney transplant patients medicated with tacrolimus[J]. Pharmacogenomics J,2010,10(2):120-125.
[11] Marju OM, Mia K, Malin KS, et al. Variants in the Calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels[J]. Diabetes, 2002, 51(8): 2658-2664.
[12] Emma C, Jenny F, Leif G, et al. Variation in the Calpain-10 gene is associated with elevated triglyceride levels and reduced adipose tissue messenger ribonucleic acid expression in obese Swedish subjects[J]. J Clin Endocrinol Metab, 2004, 89(7): 3601-3605 .
[13] Horikawa Y, Oda N, Cox NJ, et al. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus[J]. Nat Genet, 2000, 26(2):163-175.
[14] Baier LJ, Permana PA, Yang X, et al. A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance[J]. J Clin Invest, 2000, 106(7): 69-73.
[15] Malecki MT, Moczulski DK, Klupa T, et al. Homozygous combination of calpain 10 gene haplotypes is associated with type 2 diabetes mellitus in a Polish population[J]. Eur J Endocrinol, 2002, 146(5): 695-699.
[16] del Bosque-Plata L, Aguilar-Salinas CA, Tusie-Luna MT, et al. Association of the calpain-10 gene with type 2 diabetes mellitus in a Mexican population[J]. Mol Genet Metab, 2004, 81(2):122-126.
[17] Horikawa Y, Oda N, Yu L, et al. Genetic variations in calpain-10 gene are not a major factor in the occurrence of type 2 diabetes in Japanese[J]. J Clin Endocrinol Metab, 2003, 88(1): 244-247.
[18] Garant MJ, Kao WH, Brancati F, et al. SNP43 of CAPN10 and the risk of type 2 diabetes in African-Americans: the atherosclerosis risk in communities study[J]. Diabetes, 2002, 51(1): 231-237.
[19] 陈陵霞,纪立农,韩学尧,等. 2型糖尿病家系Calpain 10 基因多态性的研究[J].中华医学杂志,2003,83(21):1856-1859.