Key result
Comprehensive mutation scanning of KCNQ1 did not identify novel pathogenic mutations, and allele frequencies of variants like P448R did not differ significantly between lone AF cases and controls.
Why the study?
Does genetic variation in the KCNQ1 gene cause lone atrial fibrillation in Han Chinese patients?
Case-Control (n=376)
No
Does genetic variation in the KCNQ1 gene cause lone atrial fibrillation in Han Chinese patients?
Absolute Event Rate: 10.8% vs 8.6%
p-value: p=0.41
Comprehensive mutation scanning of KCNQ1 did not identify novel pathogenic mutations or risk-conferring polymorphisms in Han Chinese patients with lone AF, suggesting routine genetic testing is not warranted.
KCNQ1 variants unlikely to drive lone AF in Han Chinese; leaves open other loci and advises against routine testing.
OBJECTIVE: To determine the extent to which genetic variation in the potassium channel gene KCNQ1 causes atrial fibrillation (AF). DESIGN: Case-control study. SETTING: National University Hospital, Singapore. PATIENTS: Han Chinese patients (n=111) with lone AF (onset <60 years and lacking risk factors) and 265 Han Chinese controls. INTERVENTIONS: Blood draw, 12-lead electrocardiogram and transthoracic echocardiogram were performed on patients with AF at enrolment. MAIN OUTCOME MEASURES: DNA sequence variants in the coding region and exon-intron boundaries of KCNQ1 as detected by direct sequencing. RESULTS: Four previously reported coding variants were identified: I145I, S546S, P448R and G643S. An additional 19 non-coding variants were identified, nine of which are newly reported. None were predicted to create a cryptic splicing site. The allele frequencies of the two non-synonymous variants did not differ significantly in the AF cases compared with 265 Han Chinese controls (P448R: 10.8% in cases vs 8.6% in controls, p=0.41; G643S: 1.4% in cases vs 0.8% in controls, p=0.43). CONCLUSIONS: Comprehensive mutation scanning of KCNQ1 did not identify novel pathogenic mutations or risk-conferring polymorphisms. As in Caucasians, genetic variation in KCNQ1 is not a common cause of AF in Han Chinese. Routine genetic testing of KCNQ1 for AF is, therefore, not warranted.
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Chen et al. (2010) conducted a case-control in Lone atrial fibrillation (n=376). KCNQ1 genetic variation vs. Healthy Han Chinese controls was evaluated on Allele frequency of the P448R variant in KCNQ1 (p=0.41). Comprehensive mutation scanning of KCNQ1 did not identify novel pathogenic mutations, and allele frequencies of variants like P448R did not differ significantly between lone AF cases and controls.
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