Forcada Y, Holder A, Church D B, Catchpole B
Department of Clinical Sciences and Services, Royal Veterinary College, North Mymms, UK.
J Vet Intern Med. 2014 Mar-Apr;28(2):458-64. doi: 10.1111/jvim.12275. Epub 2013 Dec 26.
Feline diabetes mellitus (DM) shares many pathophysiologic features with human type 2 DM. Human genome-wide association studies have identified genes associated with obesity and DM, including melanocortin 4 receptor (MC4R), which plays an important role in energy balance and appetite regulation.
HYPOTHESIS/OBJECTIVES: To identify single nucleotide polymorphisms (SNPs) in the feline MC4R gene and to determine whether any SNPs are associated with DM or overweight body condition in cats.
Two-hundred forty domestic shorthaired (DSH) cats were recruited for the study. Of these, 120 diabetics were selected (60 overweight, 60 lean), along with 120 nondiabetic controls (60 overweight and 60 lean). Males and females were equally represented.
A prospective case-control study was performed. Genomic DNA was extracted from blood samples and used as template for PCR amplification of the feline MC4R gene. The coding region of the gene was sequenced in 10 cats to identify polymorphisms. Subsequently, genotyping by restriction fragment length polymorphism (RFLP) analysis assessed MC4R:c.92C > T allele and genotype frequencies in each group of cats.
No significant differences in MC4R:c.92C>T allele or genotype frequencies were identified between nondiabetic overweight and lean cats. In the overweight diabetic group, 55% were homozygous for the MC4R:c.92C allele, compared to 33% of the lean diabetics and 30% of the nondiabetics. The differences between the overweight diabetic and the nondiabetics were significant (P < .01).
We identified a polymorphism in the coding sequence of feline MC4R that is associated with DM in overweight DSH cats, similar to the situation in humans.
猫糖尿病（DM）与人类2型糖尿病具有许多病理生理特征。人类全基因组关联研究已鉴定出与肥胖和糖尿病相关的基因，包括黑皮质素4受体（MC4R），其在能量平衡和食欲调节中起重要作用。
假设/目的：鉴定猫MC4R基因中的单核苷酸多态性（SNP），并确定是否有任何SNP与猫的糖尿病或超重身体状况相关。
招募了240只家养短毛猫（DSH）用于该研究。其中，选择了120只糖尿病猫（60只超重，60只体重正常），以及120只非糖尿病对照猫（60只超重和60只体重正常）。雄性和雌性数量均等。
进行了一项前瞻性病例对照研究。从血液样本中提取基因组DNA，并用作猫MC4R基因PCR扩增的模板。对10只猫的基因编码区进行测序以鉴定多态性。随后，通过限制性片段长度多态性（RFLP）分析进行基因分型，评估每组猫中MC4R:c.92C>T等位基因和基因型频率。
在非糖尿病超重猫和体重正常猫之间，未发现MC4R:c.92C>T等位基因或基因型频率有显著差异。在超重糖尿病组中，55%为MC4R:c.92C等位基因纯合子，相比之下，体重正常的糖尿病猫为33%，非糖尿病猫为30%。超重糖尿病猫与非糖尿病猫之间的差异具有统计学意义（P<.01）。
我们在猫MC4R编码序列中鉴定出一种多态性，该多态性与超重DSH猫的糖尿病相关，类似于人类的情况。
