Variants in KCNQ1, AP3S1, MAN2A1, and ALDH7A1 and the risk of type 2 diabetes in the Chinese Northern Han population: a case-control study and meta-analysis.
BACKGROUND
Recent studies have explored several novel type 2 diabetes (T2D) susceptibility variants in the KCNQ1 (rs2237892), AP3S1 (rs3756555), MAN2A1 (rs2015698), and ALDH7A1 (rs2306617) genes in Japan and Western Africa. The aim here was to evaluate the contribution of variants in these genes to predisposition for T2D in the Chinese Northern Han population.


METHODS
Four candidate single-nucleotide polymorphisms (rs2237892, rs2306617, rs2015698, and rs3756555) were selected and genotyped in 537 unrelated individuals with type 2 diabetes and 510 normal controls. A meta-analysis was also done to explore the association of rs2237892 with T2D in this population.


RESULTS
The C risk allele in rs2237892 and rs3756555 conferred significantly increased susceptibility to T2D (p=0.001, p=0.003, respectively). The significant association remained after adjusting the age, sex, and BMI (OR=1.40, 95%CI: 1.16-1.69, p=0.001; OR=1.35 95%CI: 1.11-1.63, p=0.002). No association was observed in any genetic models for rs2015698 and rs2306617. Further investigation of the control subjects using an additive model showed that fasting plasma glucose was significantly higher in the individuals with the CC genotype of rs2237892 than in those with the other two genotypes after adjusting for age, sex, and BMI (beta=0.062 mmol/l per risk allele, p=0.008). The SNP of rs3756555 was marginally associated with BMI in a recessive model (p=0.05). Meta-analysis yielded an OR of 1.36 (95%CI: 1.23-1.51) for rs2237892.


CONCLUSIONS
In this study the effects of KCNQ1 and AP3S1 variants on susceptibility to T2D in the Chinese Northern Han population were confirmed.
Zhou
Jian-Bo
JB
Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Yang
Jin-Kui
JK
Zhao
Lei
L
Xin
Zhong
Z
D033963:Adaptor Protein Complex 3 / Q000235:genetics*; D034002:Adaptor Protein Complex sigma Subunits / Q000235:genetics*; D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008297:Male; D008361:Mannosidases / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012306:Risk
C115637:AP3S1 protein, human; D033963:Adaptor Protein Complex 3; D034002:Adaptor Protein Complex sigma Subunits; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D009419:Nerve Tissue Proteins; C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase; D008361:Mannosidases