Kulanuwat Sirikul, Phonrat Benjaluck, Tungtrongchitr Anchalee, Limwongse Chanin, Chongviriyaphan Nalinee, Tungtrongchitr Rungsunn, Santiprabhob Jeerunda
Southeast Asian J Trop Med Public Health. 2014 Jan;45(1):214-25.
Single nucleotide polymorphisms (SNPs) in PCSK1, namely, rs6234, rs6235, and rs271939 have been linked to obesity in European population; and rs3811951 has also been connected to type 2 diabetes and obesity parameters in Chinese population. In this family-based case-control study, we analyzed links between PCSK1 genetic variants and obesity in Thai children and their families. Eleven obese children with a percent weight for height > or = 140 who had family history of obesity and 69 family members were recruited. SNPs rs6234, rs6235, rs3811951, and rs271939 of PCSK1 were analyzed using PCR and gene sequencing methods. DNA of 200 normal weight subjects was used as control. Participants with variant genotypes in the rs6234-6235 pair are at significantly more risk of being obese [OR = 2.44 (1.35-4.43), p = 0.003], and also at increased risk of being severely obese (obese class III) [OR = 3.03 (1.20-7.66), p = 0.015]. Variant rs3811951 showed no association with being obese, but is significantly linked to an increased risk of being severely obese [OR = 3.59 (1.42-9.08) p = 0.005]. Moreover, high density lipoprotein (HDL)-C levels between normal and variant rs3811951 group differed considerably, with patients with variant genotype having a lower HDL-C level (p = 0.037). Thus, Thais carrying SNPs rs6234-5 are at increased risk of being obese, and the risk of severe obesity increases when carrying both rs6234-5 and rs3811951, but not with rs271939. Furthermore, patients with genetic variations at rs3811951 are at risk of having low HDL-C levels.
前蛋白转化酶枯草溶菌素1（PCSK1）中的单核苷酸多态性（SNP），即rs6234、rs6235和rs271939，已被证明与欧洲人群的肥胖有关；而rs3811951也与中国人群的2型糖尿病和肥胖参数有关。在这项基于家庭的病例对照研究中，我们分析了PCSK1基因变异与泰国儿童及其家庭肥胖之间的联系。招募了11名身高体重百分比≥140且有肥胖家族史的肥胖儿童及其69名家庭成员。采用聚合酶链反应（PCR）和基因测序方法分析PCSK1的SNP rs6234、rs6235、rs3811951和rs271939。以200名正常体重受试者的DNA作为对照。rs6234 - 6235位点具有变异基因型的参与者肥胖风险显著增加[比值比（OR）= 2.44（1.35 - 4.43），p = 0.003]，严重肥胖（III级肥胖）风险也增加[OR = 3.03（1.20 - 7.66），p = 0.015]。rs3811951变异与肥胖无关联，但与严重肥胖风险显著相关[OR = 3.59（1.42 - 9.08），p = 0.005]。此外，rs3811951正常组与变异组之间的高密度脂蛋白（HDL）- C水平差异显著，变异基因型患者的HDL - C水平较低（p = 0.037）。因此，携带rs6234 - 5 SNP的泰国人肥胖风险增加，同时携带rs6234 - 5和rs3811951时严重肥胖风险增加，但rs271939无此关联。此外，rs3811951存在基因变异的患者有HDL - C水平降低的风险。
